Clinical Focus

  • Anatomic/Clinical Pathology

Academic Appointments

  • Assistant Professor - Med Center Line, Pathology

Professional Education

  • Fellowship:Brigham and Women's Hospital Harvard Medical School (2009) MA
  • Residency:Brigham and Women's Hospital Harvard Medical School (2008) MA
  • Medical Education:UCSD School of Medicine (2005) CA
  • Residency:Stanford Hospital and Clinics (2010) CA
  • Board Certification: Anatomic/Clinical Pathology, American Board of Pathology (2011)

Research & Scholarship

Current Research and Scholarly Interests

My research interest is in gynecologic and obstetric pathology, specifically in ovarian and endometrial malignancies and placental clinical-pathologic disorders.


All Publications

  • Variable color Doppler sonographic appearances of retained products of conception: radiologic-pathologic correlation. Abdominal imaging Kamaya, A., Krishnarao, P. M., Folkins, A. K., Jeffrey, R. B., Desser, T. S., Maturen, K. E. 2015


    Retained products of conception (RPOC) displays variable vascularity, ranging from avascular to markedly vascular on color Doppler sonography. We hypothesize that variability in sonographic vascularity may be due to histopathologic variation in the placental tissue.After institutional review board approval, sonographic images and pathologic specimens were retrospectively reviewed in 26 patients with pathologically proven RPOC. Ultrasound (US) images were scored 0-3 for the degree of vascularity by two radiologists blinded to the diagnosis. Corresponding pathologic specimens were evaluated for vascularization of chorionic villi, degree of inflammation, morphology of maternal arteries, chorionic villous preservation, and percentage of clot, membranes, chorionic villi, and decidua/myometrium. Statistical analysis, including multiple linear regression, was performed.RPOC with histologically avascular chorionic villi or those with markedly reduced vascularization had significantly lower US vascularity scores (p = 0.030) than those with chorionic villi showing normal or decreased vascularization. Sonographically avascular RPOC had a significantly lower percentage villi (p = 0.028) and higher percentage of decidua (p = 0.004) than specimens where US showed any Doppler vascularity. Histologic vascularity of villi (p = 0.049) and non-observation of maternal arteries (p = 0.001) were significant predictors of US vascularity scores in multivariate linear regression analysis, while inflammation of villi (p = 0.053) was a marginally significant predictor.Histologic vascularity of villi appears to contribute to the observed variation in sonographic vascularity. This finding may underlie known differences in clinical outcomes between sonographic vascularity groups.

    View details for DOI 10.1007/s00261-015-0424-x

    View details for PubMedID 25862548

  • Prenatal hydrops foetalis associated with infantile free sialic acid storage disease. Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology Chock, V. Y., Milan, K. E., Folkins, A. K., Hazard, F. K., Bernstein, J. A., Hintz, S. R. 2015: 1-2

    View details for DOI 10.3109/01443615.2015.1017558

    View details for PubMedID 26076308

  • Cost and turn-around time display decreases inpatient ordering of reference laboratory tests: a time series BMJ QUALITY & SAFETY Fang, D. Z., Sran, G., Gessner, D., Loftus, P. D., Folkins, A., Christopher, J. Y., Shieh, L. 2014; 23 (12): 994-1000
  • Risk of Secondary Malignancy (Including Breast) in Patients With Mismatch-repair Protein Deficiency AMERICAN JOURNAL OF SURGICAL PATHOLOGY Clay, M. R., Allison, K. H., Folkins, A. K., Longacre, T. A. 2014; 38 (11): 1494-1500
  • Evaluation of serial urine viral cultures for the diagnosis of cytomegalovirus infection in neonates and infants. Pediatric and developmental pathology Chisholm, K. M., Aziz, N., McDowell, M., Guo, F. P., Srinivas, N., Benitz, W. E., Norton, M. E., Gutierrez, K., Folkins, A. K., Pinsky, B. A. 2014; 17 (3): 176-180


    Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide. Urine viral culture is the standard for CMV diagnosis in neonates and infants. The objectives of this study were to compare the performance of serial paired rapid shell vial cultures (SVC) and routine viral cultures (RVC), and to determine the optimal number of cultures needed to detect positive cases. From 2001 to 2011, all paired CMV SVC and RVC performed on neonates and infants less than 100 days of age were recorded. Testing episodes were defined as sets of cultures performed within 7 days of one another. A total of 1264 neonates and infants underwent 1478 testing episodes; 68 (5.4%) had at least one episode with a positive CMV culture. In episodes where CMV was detected before day 21 of life, the first specimen was positive in 100% (16/16) of cases. When testing occurred after 21 days of life, the first specimen was positive in 82.7% (43/52) of cases, requiring three cultures to reach 100% detection. The SVC was more prone to assay failure than RVC. Overall, when RVC was compared to SVC, there was 86.0% positive agreement and 99.9% negative agreement. In conclusion, three serial urine samples are necessary for detection of CMV in specimens collected between day of life 22 and 99, while one sample may be sufficient on or before day of life 21. Though SVC was more sensitive than RVC, the risk of SVC failure supports the use of multimodality testing to optimize detection.

    View details for DOI 10.2350/14-01-1432-OA.1

    View details for PubMedID 24617645

  • Diagnosis of Congenital CMV Using PCR Performed on Formalin-fixed, Paraffin-embedded Placental Tissue AMERICAN JOURNAL OF SURGICAL PATHOLOGY Folkins, A. K., Chisholm, K. M., Guo, F. P., McDowell, M., Aziz, N., Pinsky, B. A. 2013; 37 (9): 1413-1420


    Congenital cytomegalovirus (CMV) infection may be asymptomatic until hearing loss manifests in childhood. Because diagnosis of congenital CMV requires viral detection within an infant's first 21 days of life, CMV polymerase chain reaction (PCR) on formalin-fixed, paraffin-embedded (FFPE) placental tissue provides a unique opportunity to identify congenital exposure in cases in which CMV is not initially suspected. To assess the utility of this approach, a database of all CMV cultures performed from July 2001 to March 2012 was used to identify infants in whom urine CMV cultures were obtained within 100 days of life. Corresponding placentas were then identified through the pathology database. The database was also queried to identify placentas in which CMV immunohistochemical analysis had been performed. CMV PCR was positive in FFPE placental tissue from 100% (5/5) of cases in which the first urine culture collected before the first 21 days of life was positive. Placentas from 20 infants with negative CMV urine cultures were CMV PCR negative. Interestingly, CMV was detected in 12.5% (1/8) of placentas in which the first CMV-positive urine culture was collected after the first 21 days of life. Furthermore, 4% (1/26) of placentas with chronic villitis by histology (no urine cultures available) were CMV PCR positive. In the 10 CMV PCR-positive placentas, including 3 cases of fetal demise, CMV immunohistochemistry was positive in just 6 cases. These results suggest that the confirmation of CMV exposure in utero by PCR of FFPE placental tissue provides a useful adjunct to histologic evaluation and may identify infants requiring close clinical follow-up.

    View details for Web of Science ID 000330429800016

  • Hereditary gynaecological malignancies: advances in screening and treatment HISTOPATHOLOGY Folkins, A. K., Longacre, T. A. 2013; 62 (1): 2-30


    In the last two decades there have been significant advances in our understanding of female genital tract tumours. The discovery of BRCA1 and BRCA2 genes in ovarian cancer and the mismatch repair genes in endometrial carcinoma has revolutionized our approach to the diagnosis and screening of women for ovarian and uterine cancers. This review discusses the pathogenesis of these two hereditary syndromes in depth and explains how the molecular genetics is tailoring the manner in which these diseases are diagnosed and potentially treated. Other, less common hereditary conditions associated with gynaecological tract manifestations, such as Cowden syndrome, Peutz-Jeghers syndrome, Gorlin syndrome and hereditary leiomyomatosis and renal cell carcinoma, are also summarized briefly.

    View details for DOI 10.1111/his.12028

    View details for Web of Science ID 000312533600002

    View details for PubMedID 23240667

  • The impact of tissue block sampling on the detection of p53 signatures in fallopian tubes from women with BRCA 1 or 2 mutations (BRCA+) and controls MODERN PATHOLOGY Mehra, K. K., Chang, M. C., Folkins, A. K., Raho, C. J., Lima, J. F., Yuan, L., Mehrad, M., Tworoger, S. S., Crum, C. P., Saleemuddin, A. 2011; 24 (1): 152-156


    The tubal p53 signature is a putative precursor to pelvic serous carcinoma, but its frequencies in women with inherited mutations in the BRCA1 or BRCA2 genes (BRCA+) and controls has been controversial. An initial section and two levels (100-200??m) from every block in BRCA+ (24) and control tubes (40) were stained for p53. The frequency of p53 signatures was computed between the populations and across the three levels from each block, and analyzed by Fisher exact test. A total of 17 (71%) BRCA+ and 20 (50%) control tubes were p53 signature positive (P=0.12); 21 and 16% of all tissue blocks sectioned harbored signatures (P=0.29), and 76 and 67% were found in the fimbria. In 49 and 32% of p53 signature positive cases in the two groups, the p53 signatures were not discovered until the second or third round of sectioning. In all, 38 and 40% of BRCA+ and control subjects harbored p53 signatures in more than one focus in a single block. In one case (BRCA+), a highly atypical proliferation was identified in one serial section. The p53 signatures are more common than previously reported and the frequency of detection increases as a function of sectioning through the tissue block, both in absolute frequency and in numbers of p53 signatures detected in a given block. There is a trend for a higher absolute frequency of p53 signatures (71 vs 50%; P=0.12) in BRCA+ subjects, but this is not reflected in a greater average number of p53 signatures or positive blocks per case. This study underscores the importance of systematic immunohistochemical examination of fallopian tubes when conducting epidemiological studies that compare the frequency of p53 signatures in different populations. Attention to this detail is critical when exploring risk factors germane to early serous carcinogenesis.

    View details for DOI 10.1038/modpathol.2010.171

    View details for Web of Science ID 000285868900017

    View details for PubMedID 20871594

  • Evaluation of vascular space involvement in endometrial adenocarcinomas: laparoscopic vs abdominal hysterectomies Folkins, A. K., Nevadunsky, N. S., Saleemuddin, A., Jarboe, E. A., Muto, M. G., Feltmate, C. M., Crum, C. P., Hirsch, M. S. NATURE PUBLISHING GROUP. 2010: 1073-1079


    Recent reports have described 'vascular pseudoinvasion' in total laparoscopic hysterectomies with endometrial carcinoma. To better understand this phenomenon, we compared pathologic findings in these laparoscopic and total abdominal hysterectomies performed for uterine endometrioid adenocarcinoma. Reports from 58 robotically assisted laparoscopic and 39 abdominal hysterectomies with grade 1 or 2 endometrioid endometrial adenocarcinomas were reviewed for stage, depth of invasion, vascular space involvement, uterine weight, and lymph node metastases. In addition, attention was given to possible procedural artifacts, including vertical endomyometrial clefts, and inflammatory debris, benign endometrial glands, and disaggregated tumor cells in vascular spaces. All foci with vascular involvement were reviewed by three gynecologic pathologists. Nine of the 58 (16%) laparoscopic and 3 of the 39 (7%) abdominal hysterectomies contained vascular space involvement based on the original pathology reports (P-value=0.0833). No one histologic feature consistently distinguished laparoscopic from abdominal cases on blind review of the available cases. Disaggregated intravascular tumor cells were significantly associated with reported vascular involvement in both procedures (P-values<0.001 and 0.016), most of which were corroborated on review. Laparoscopic procedures tend to have a higher index of vascular involvement, which is associated with lower stage, fewer lymph node metastases, and less myometrial invasion; however, pathologists cannot consistently determine the procedure on histologic findings alone. Moreover, there is significant inter-observer variability in distinguishing true from artifactual vascular space involvement, even among pathologists at the same institution. The clinical significance of apparent true vascular space involvement seen adjacent to artifacts is unclear, as is the impact of laparoscopic hysterectomy on recurrence risk.

    View details for DOI 10.1038/modpathol.2010.91

    View details for Web of Science ID 000280563900005

    View details for PubMedID 20473276

  • Utility of Chromosomal Chromogenic in Situ Hybridization as an Alternative to Flow Cytometry and Cytogenetics in the Diagnosis of Early Partial Hydatidiform Moles A Validation Study Folkins, A., Cruz, L., Goldstein, D. P., Berkowitz, R. S., Crum, C., Kindelberger, D. SCI PRINTERS & PUBL INC. 2010: 275-278


    The introduction of p57 immunohistochemistry has aided the distinction between early complete moles (CMs) and hydropic abortus (HA), but no single technique has emerged for the distinction between early partial moles (PMs) and HA. Flow cytometry and cytogenetics have been used, but these require specialized equipment/expertise. The goal of this study is validation of chromosome in situ hybridization (CrISH), focusing on comparing the results to those obtained by cytogenetic methods.Archival paraffin blocks from molar and nonmolar gestations were retrieved. Sections were labeled with a chromosome 10 probe. Hybridization and visualization were performed using standard protocols. One hundred nuclei per sample were scored for the number ofsignals.Of 50 hydatidiform moles, 22 were PMs and 28 were CMs. The CMs showed 2 signals in 25 cases and 4 signals in 3 cases. The PMs showed 3 signals in 21 cases and 2 signals in 1 case. For the HAs there were 2 signals in 24 cases, and 1 case had 3 signals. Concordance between CrISH and flow cytometry studies for molar gestations was 95%.CrlSH is a highly effective adjunct in differentiating between PM and CM and between PM and HA. CrlSH is a simple, cost effective adjunct in evaluating molar gestations.

    View details for Web of Science ID 000280968800002

    View details for PubMedID 20795338

  • Tubal and ovarian pathways to pelvic epithelial cancer: a pathological perspective HISTOPATHOLOGY Jarboe, E. A., Folkins, A. K., Drapkin, R., Ince, T. A., Agoston, E. S., Crum, C. P. 2009; 55 (5): 619-619
  • Epidemiologic correlates of ovarian cortical inclusion cysts (CICs) support a dual precursor pathway to pelvic epithelial cancer GYNECOLOGIC ONCOLOGY Folkins, A. K., Saleemuddin, A., Garrett, L. A., Garber, J. E., Muto, M. G., Tworoger, S. S., Crum, C. P. 2009; 115 (1): 108-111


    Many ovarian carcinomas are presumed to arise within ovarian cortical inclusion cysts (CICs). This study examined the frequency of ovarian CICs in relation to epidemiologic risk factors in women with BRCA1 and BRCA2 (BRCA+) mutations.BRCA+ women who underwent risk-reducing bilateral salpingo-oophorectomy were studied (n=74). Fifteen demographic variables (e.g., age at time of surgery, age at first birth, age at menopause, body mass index (BMI), gravidity) from a review of the medical records and three pathologic variables (cystic and atretic follicles, corpora lutea) were recorded. Statistical associations were made using T-test or Chi Square analysis and logistic regression analysis for p-trend.Women whose ovaries contained 7 for more CICs were older at first birth (p=0.034), surgery (p=0.059), menopause (p=0.046) and had a higher BMI (p=0.034) than those with <7 CICs. Regression analysis revealed a significant association between CICs and increasing BMI (p=0.01).CICs correlate with greater body mass index, similar to low-grade serous and endometrioid tumors and in contrast to high-grade serous carcinoma and its putative precursor in the fallopian tube. A model is presented for ovarian and tubal pathways to pelvic cancer that are linked to different microscopic precursors with distinct epidemiologic correlates.

    View details for DOI 10.1016/j.ygyno.2009.06.032

    View details for Web of Science ID 000269965700021

    View details for PubMedID 19615727

  • Intercepting early pelvic serous carcinoma by routine pathological examination of the fimbria MODERN PATHOLOGY Semmel, D. R., Folkins, A. K., Hirsch, M. S., Nucci, M. R., Crum, C. P. 2009; 22 (8): 985-988


    Recent evidence indicates that the distal fallopian tube is the principal site of early serous cancer in women with a hereditary risk for ovarian cancer. Moreover, the fimbria is involved by early cancer in a significant minority of pelvic serous carcinomas, irrespective of whether the patient has a hereditary BRCA1 or BRCA2 mutation. In addition, the distal tube has been identified occasionally as a site of concurrent endometrioid tumors in women with endometrial carcinoma. Although the risk of sporadic fimbrial tumors in otherwise healthy women without genetic risk is unknown, routine histological examination of the fimbria provides the opportunity to determine the risk of such an event. To illustrate this point, a case of a woman who underwent surgery for an ovarian fibroma is presented. The distal tube was submitted, and found to harbor a focus of serous tubal intraepithelial carcinoma (STIC) with a 2-mm invasive tumor. Incidentally discovered carcinomas underscore the potential risk, albeit low, of concurrent unsuspected malignancy in the distal fallopian tube and emphasize the importance of routine pathological examination of the fimbria in all salpingectomies. The rationale for this strategy, and its potential effect on early detection and in uncovering persons or families potentially at risk for ovarian cancer, is discussed.

    View details for DOI 10.1038/modpathol.2009.64

    View details for Web of Science ID 000268540400001

    View details for PubMedID 19407856

  • Precursors to pelvic serous carcinoma and their clinical implications GYNECOLOGIC ONCOLOGY Folkins, A. K., Jarboe, E. A., Roh, M. H., Crum, C. P. 2009; 113 (3): 391-396


    Pelvic serous carcinoma has traditionally been viewed as a rapidly evolving malignancy, due principally to its late stage at diagnosis and tendency for poor outcome, both in the endometrium and the upper genital tract. Recently, studies of women with BRCA1 or BRCA2 mutations (BRCA+) undergoing risk reducing salpingo-oophorectomy have highlighted the distal fallopian tube as a common (80%) site of tumor origin and additional studies of unselected women with pelvic serous carcinoma have demonstrated that serous tubal intraepithelial carcinoma may precede a significant percentage of these tumors. This review examines the serous carcinogenic spectrum in the fallopian tube, highlighting recent evidence that these tumors may follow a defined precursor that has been present for a prolonged interval. The data supporting a candidate precursor, the implications of these findings for early detection and prevention of pelvic serous carcinoma and the caveats, are discussed.

    View details for DOI 10.1016/j.ygyno.2009.01.013

    View details for Web of Science ID 000266320300019

    View details for PubMedID 19237187

  • Risk factors for a serous cancer precursor ("p53 signature") in women with inherited BRCA mutations GYNECOLOGIC ONCOLOGY Saleemuddin, A., Folkins, A. K., Garrett, L., Garber, J., Muto, M. G., Crum, C. P., Tworoger, S. 2008; 111 (2): 226-232


    Pelvic (ovarian) serous carcinomas frequently contain p53 mutations. Recently, a candidate serous cancer precursor (the p53 signature) with p53 mutations and other features in common with serous cancer has been discovered in distal fallopian tube mucosa. This study examined the relationship of putative ovarian cancer risk factors with the presence of p53 signatures in women with BRCA mutations (BRCA+).Fallopian tubes from 75 BRCA+ women were immunostained for p53 signatures and correlated with age at first childbirth, parity, oral contraceptive use, body mass index (BMI), and BRCA subtype (1 or 2). Statistical analysis was performed with the T-test or Chi-square analysis and logistic regression adjusting for age and parity.Thirty-eight percent of the tubes contained p53 signatures, which were significantly associated with older age at first childbirth (mean 30.8 vs. 28.4 years; p=0.04) and lower parity (mean 1.4 vs. 2.2; p=0.01) in univariate analyses. The unadjusted odds ratios were 3.8 (p-trend=0.04) for first childbirth>/=30 years versus <30 and 0.2 (p-trend=0.01) for parity >/= 3 versus nulliparous women. After adjusting for age and parity, the trend for age at first childbirth became non-significant (adjusted odds ratio 3.5; p-trend=0.15), while that for parity remained significant (adjusted odds ratio 0.2; p-trend 0.02).The p53 signature is significantly associated with lower parity and possibly higher age at first childbirth, further linking this entity to serous cancer via risk factors associated with ovulation. The p53 signature merits consideration as a surrogate marker for serous cancer risk.

    View details for DOI 10.1016/j.ygyno.2008.07.018

    View details for Web of Science ID 000260987700012

    View details for PubMedID 18718648

  • Tubal and ovarian pathways to pelvic epithelial cancer: a pathological perspective HISTOPATHOLOGY Jarboe, E. A., Folkins, A. K., Drapkin, R., Ince, T. A., Agoston, E. S., Crum, C. P. 2008; 53 (2): 127-138


    Prolongation of ovarian epithelial cancer survival depends on early detection or improved responses to chemotherapy. Gains in either have been modest at best. Understanding the diverse pathogenesis of this disease is critical to early intervention or prevention. This review addresses six important variables, including (i) cell of origin, (ii) site of origin, (iii) initial genotoxic events, (iv) risks imposed by hereditary and other promoting conditions, (v) subsequent factors that promote different patterns of metastatic spread, and (vi) prospects for intervention. This review proposes two distinct pathways to pelvic epithelial cancer. The first initiates in ovarian surface epithelium (OSE), Mullerian inclusions or endometriosis in the ovary. The second arises from the endosalpinx and encompasses a subset of serous carcinomas. The serous carcinogenic sequence in the distal fallopian tube is described and contrasted with lower grade serous tumors based on tumour location, earliest genetic change and ability (or lack of) to undergo terminal (ciliated) differentiation. Ultimately, a clear understanding of tumour origin and the mechanism(s) leading to the earliest phases of the serous and endometrioid carcinogenic sequences may hold the greatest promise for designing prevention strategies and/or developing new therapies.

    View details for DOI 10.1111/j.1365-2559.2007.02938.x

    View details for Web of Science ID 000258504400001

    View details for PubMedID 18298580

  • Adenofibroma of the fimbria: A common entity that is indistinguishable from ovarian adenofibroma INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY Bossuyt, V., Medeiros, F., Drapkin, R., Folkins, A. K., Crum, C. P., Nucci, M. R. 2008; 27 (3): 390-397


    Fallopian tube adenofibromas (FTAs) are considered rare, but their frequency has never been determined by systematic sampling of this organ. To determine the morphological spectrum and prevalence of FTAs, we analyzed a consecutive series of fallopian tubes removed during surgery for a wide range of disorders. Fallopian tubes were completely evaluated with attention to the fimbriated end (sectioning and extensively examining the fimbria [SEE-FIM] protocol). Discrete localized subepithelial stromal proliferations with alterations in plical architecture and a glandular component were classified as FTAs. Fallopian tube adenofibromas less than 3 mm were classified as incipient adenofibromas (iFTAs). The association of FTAs with ovarian adenofibromas (OAs) was also evaluated. Twenty-six of 28 (30% overall frequency) consecutively examined bilateral fallopian tube specimens contained adenofibromas (FTAs and iFTAs); all confined to the fimbria. Twelve FTAs were identified (11 cases; 14% frequency), 3 of which exceeded 1 cm. Twenty-nine iFTAs were identified (18 cases; 20% frequency); iFTAs were multiple in 10, bilateral in 4, and associated with an FTA in 3 cases. Three (25%) of 12 OAs with completely examined fallopian tubes were associated with FTAs. Stroma in both iFTAs and FTAs was CD10 and inhibin positive, and the epithelial phenotype of both iFTAs and OAs was identical, composed of secretory and ciliated cells. The fimbrial endosalpinx and the ovarian cortex share the potential for similar specialized stromal expansions with the formation of biphasic tumors with endosalpingeal epithelial differentiation. Similar to reports of serous and endometrioid tumors in both the distal fallopian tube and ovary, FTAs highlight a shared epithelial-mesenchymal differentiation pathway in the fimbrial-ovarian region. Whether the shared tumor phenotype in these 2 organs is coincidental or interdependent bears further investigation.

    View details for DOI 10.1097/PGP.0b013e3181639a82

    View details for Web of Science ID 000257277900010

    View details for PubMedID 18580316

  • A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and fallopian tubes from women with BRCA mutations GYNECOLOGIC ONCOLOGY Folkins, A. K., Jarboe, E. A., Saleemuddin, A., Lee, Y., Callahan, M. J., Drapkin, R., Garber, J. E., Muto, M. G., Tworoger, S., Crum, C. P. 2008; 109 (2): 168-173


    Early serous carcinomas predominate in the fimbria of women with BRCA mutations (BRCA+). An entity in non-neoplastic mucosa sharing several properties of early serous carcinomas--the "p53 signature"--has been described in the distal fallopian tube and proposed as a precursor to serous carcinomas. This study compared the prevalence of p53 signatures in ovarian cortical inclusion cysts (CICs) and fallopian tubes from BRCA+ women and explored their relationship.All tissues from 75 completely excised ovaries and tubes obtained during prophylactic surgery were studied by conventional microscopy, immunostaining for p53, and in selected cases, gamma-H2AX (DNA damage). P53 signatures were defined as 12 or more consecutive p53-positive secretory cell nuclei. Their prevalence in fallopian tubes and CICs was recorded, compared to an existing database of consecutive women without a suspicion of BRCA+ or ovarian cancer, and correlated with the number of CICs.Tubal p53 signatures were detected in 29 of 75 cases (38%); 20 of 30 (66%) signatures examined were gamma-H2AX-positive. One ovary contained a small gamma-H2AX negative p53 signature on the ovarian surface; no p53 signatures were identified in CICs. The prevalence of BRCA+ p53 tubal signatures was similar to that of women with unknown BRCA status (38 v 33%). Presence of p53 signatures did not correlate with number of CICs.p53 signatures were common in the fallopian tubes of BRCA+ women, were not identified in CICs, and did not correlate with the latter. The tubal p53 signature merits serious consideration as an important early event in serous carcinogenesis in BRCA+ women.

    View details for DOI 10.1016/j.ygyno.2008.01.012

    View details for Web of Science ID 000256205600004

    View details for PubMedID 18342932

  • Serous carcinogenesis in the fallopian tube: A descriptive classification INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY Jarboe, E., Folkins, A., Nucci, M. R., Kindelberger, D., Drapkin, R., Miron, A., Lee, Y., Crum, C. P. 2008; 27 (1): 1-9


    The fimbria is the most common site of early serous cancer (tubal intraepithelial carcinoma or STIC) in women with BRCA mutations (BRCA+). A candidate serous cancer precursor--the p53 signature--has been found in nonneoplastic secretory cells of the fimbria, suggesting serous carcinogenesis in the tube (SCAT). This study surveyed fallopian tubes from 3 populations to characterize the morphological and immunohistochemical correlates of SCAT. The SCAT sequence was defined by strong nuclear p53 staining and DNA damage (gamma-H2AX+) in secretory cells and subdivided morphologically by (1) degree of nuclear stratification, (2) proliferative index, and (3) degree of disorganized growth. Fallopian tubes from women without a current ovarian cancer, women with BRCA mutations, and women with a coexisting pelvic serous cancer were completely examined. p53 signatures exhibited cuboidal to pseudostratified, polarized p53+ epithelial segments with variable nuclear enlargement and a MiB1 index of 0% to 30%. Tubal intraepithelial carcinomas contained from single (uncommon) to multilayered, poorly polarized, uninterrupted neoplastic cell populations that completely displaced the normal mucosa; MiB1 index exceeded 45% and was usually more than 70%. An uncommon third category, p53-positive foci with features intermediate between p53 signatures and STICs, exhibited preserved epithelial polarity, pseudostratification, incomplete replacement of the adjacent normal ciliated cells, and a MiB1 index between 40% and 75%. Transitions from 1 category to another were documented. Combined with recent reports associating STICs with pelvic serous cancer, this continuum of epithelial change validates the SCAT sequence and the fimbrial secretory cell as the site of origin for many serous carcinomas.

    View details for DOI 10.1097/pgp.0b013e31814b191f

    View details for Web of Science ID 000252124400001

    View details for PubMedID 18156967

  • Improving the Deaf community's access to prostate and testicular cancer information: a survey study BMC PUBLIC HEALTH Folkins, A., Sadler, G. R., Ko, C., Branz, P., Marsh, S., Bovee, M. 2005; 5


    Members of the Deaf community face communication barriers to accessing health information. To resolve these inequalities, educational programs must be designed in the appropriate format and language to meet their needs.Deaf men (102) were surveyed before, immediately following, and two months after viewing a 52-minute prostate and testicular cancer video in American Sign Language (ASL) with open text captioning and voice overlay. To provide the Deaf community with information equivalent to that available to the hearing community, the video addressed two cancer topics in depth. While the inclusion of two cancer topics lengthened the video, it was anticipated to reduce redundancy and encourage men of diverse ages to learn in a supportive, culturally aligned environment while also covering more topics within the partnership's limited budget. Survey data were analyzed to evaluate the video's impact on viewers' pre- and post-intervention understanding of prostate and testicular cancers, as well as respondents' satisfaction with the video, exposure to and use of early detection services, and sources of cancer information.From baseline to immediately post-intervention, participants' overall knowledge increased significantly, and this gain was maintained at the two-month follow-up. Men of diverse ages were successfully recruited, and this worked effectively as a support group. However, combining two complex cancer topics, in depth, in one video appeared to make it more difficult for participants to retain as many relevant details specific to each cancer. Participants related that there was so much information that they would need to watch the video more than once to understand each topic fully. When surveyed about their best sources of health information, participants ranked doctors first and showed a preference for active rather than passive methods of learning.After viewing this ASL video, participants showed significant increases in cancer understanding, and the effects remained significant at the two-month follow-up. However, to achieve maximum learning in a single training session, only one topic should be covered in future educational videos.

    View details for DOI 10.1186/1471-2458-5-63

    View details for Web of Science ID 000230793200001

    View details for PubMedID 15938751

  • Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma? CANCER Gandour-Edwards, R., Lara, P. N., Folkins, A. K., LaSalle, J. M., Beckett, L., Li, Y. J., Meyers, F. J., DeVere-White, R. 2002; 95 (5): 1009-1015


    Muscle-invasive urothelial carcinoma of the bladder is a highly lethal malignancy, particularly in the setting of locally advanced or metastatic disease. Prior reports of HER2/neu (c-erbB-2 or HER2) expression in bladder carcinoma have been mixed; therefore, its value in predicting metastasis or response to therapy has not been established in this tumor type. Thus, the authors evaluated a possible correlation between HER2 expression in patients with high-grade, muscle-invasive urothelial carcinoma of the bladder and outcome in patients who received paclitaxel-based chemotherapy.Archival tumor tissues from patients with advanced urothelial carcinoma who were enrolled on two clinical trials of paclitaxel-based chemotherapy regimens were analyzed for HER2/neu expression by immunohistochemistry (IHC). The authors correlated HER2 expression by IHC with clinical outcomes, such as response rate, progression free survival, and overall survival, using univariate analysis.Thirty-nine tumor specimens were assessed for HER2 expression, most of which (70%) were collected from patients with metastatic disease. All were high-grade urothelial carcinomas (transitional cell carcinomas, Grade 3). Strong HER2 expression (2+/3+) was seen in 28 patients (71%). Patients with responding disease had an HER2 expression rate of 78%, similar to the rate seen in patients with stable disease (75%). In contrast, patients with progressive disease had an HER2 expression rate of 50%, although this difference did not reach statistical significance. However, univariate analysis showed that increased HER2 expression predicted an improvement in progression free and overall survival. When HER2 status was used as a dichotomous variable, tumors with positive HER2 expression did not have any association with response or with progression free survival; however, positive HER2 status was associated significantly with a decreased risk of death (P = 0.03).This study of HER2 expression in bladder carcinoma focused on patients who were treated prospectively in a standardized fashion, unlike prior studies that have evaluated banked, archival specimens. The authors confirmed the findings of others that high-grade, muscle-invasive urothelial carcinoma of the bladder has a significant rate of HER2 expression (71%). However, contrary to other reports, the current study found that HER2 expression in the context of paclitaxel-based chemotherapy decreased the risk of death significantly. Further research is warranted on the possible association of HER2 expression with chemosensitivitiy in urothelial carcinoma as well as the efficacy of HER2-targeted therapies (such as trastuzumab) for patients with high-grade, muscle-invasive urothelial carcinoma of the bladder.

    View details for DOI 10.1002/cncr.10808

    View details for Web of Science ID 000177606000009

    View details for PubMedID 12209684

Stanford Medicine Resources: