CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Müllerian precursor lesions in serous ovarian cancer patients
Serous ovarian cancer is suggested to develop from epithelium embryologically derived from the Müllerian ducts. The authors conducted a study to thoroughly analyze the epithelium derived from those ducts (cervix, endometrium, and fallopian tubes) in serous ovarian cancer patients. Sixty women diagnosed with serous ovarian carcinoma were included in this multicenter, observational study. Tissues were embedded completely for histological assessment in accordance with the SEE-Fim (Sectioning and Extensively Examining the Fimbriated End) and SEE-End (Sectioning and Extensively Examining the Endometrium) protocols, and the prevalence of cervical, endometrial, and tubal pathology was analyzed. In 31 (52 percent) cases, a pathologic lesion was identified, and in 16 (27 percent) of these cases, coexistence of pathologic lesions was noted. Severe dysplasia was found in the cervix in one case. Endometrial intraepithelial carcinoma was found in nine (15 percent) cases; endometrial atypical hyperplasia in 19 (32 percent) cases; and serous tubal intraepithelial carcinoma in 23 (43 percent) cases. Serous tubal intraepithelial carcinoma was significantly more often concurrent with endometrial atypical hyperplasia or endometrial intraepithelial carcinoma than with benign endometrium (64 versus 28 percent; P=0.01). The authors concluded that histological assessment of epithelium derived from Müllerian ducts of serous ovarian cancer patients resulted in the identification of endometrial intraepithelial carcinoma, serous tubal intraepithelial carcinoma, or endometrial atypical hyperplasia in more than half of cases. Coexistence of these pathologic lesions was common and might represent an effect of field carcinogenesis or tumor implantation of migrating cells.
Mingels MJ, van Ham MA, de Kievit IM, et al. Müllerian precursor lesions in serous ovarian cancer patients: using the SEE-Fim and SEE-End protocol. Mod Pathol. 2014;27:1002–1013.
Correspondence: Dr. M. J. J. M. Mingels at m.mingels@obgyn.umcn.nl
Loss of 5-hydroxymethylcytosine and increasing morphologic dysplasia in melanocytic tumors
DNA methylation is the most well-studied epigenetic modification in cancer biology. The epigenetic mark 5-hydroxymethylcytosine can be converted from 5-methylcytosine by the ten-eleven translocation gene family. The authors recently reported the loss of 5-hydroxymethylcytosine in melanoma compared with benign nevi and suggested that loss of this epigenetic marker is correlated with tumor virulence based on its association with a worse prognosis. In this study, they further characterized the immunoreactivity patterns of 5-hydroxymethylcytosine in the full spectrum of melanocytic lesions to further validate the potential practical application of this epigenetic marker. They evaluated 175 cases: 18 benign nevi, 20 dysplastic nevi (10 low-grade and 10 high-grade lesions), 10 atypical Spitz nevi, 20 borderline tumors, five melanomas arising within nevi, and 102 primary melanomas. Progressive loss of 5-hydroxymethylcytosine from benign dermal nevi to high-grade dysplastic nevi to borderline melanocytic neoplasms to melanoma was observed. In addition, an analysis of the relationship of nuclear diameter with 5-hydroxymethylcytosine staining intensity within lesional cells revealed a significant correlation between larger nuclear diameter and decreased levels of 5-hydroxymethylcytosine. Furthermore, borderline lesions exhibited a diverse spectrum of staining of each individual case. The authors concluded that this study further substantiates the association of 5-hydroxymethylcytosine loss with dysplastic cytomorphologic features and tumor progression and supports the classification of borderline lesions as a biologically distinct category of melanocytic lesions.
Larson AR, Dresser KA, Zhan Q, et al. Loss of 5-hydroxymethylcytosine correlates with increasing morphologic dysplasia in melanocytic tumors. Mod Pathol. 2014;27:936–944.
Correspondence: Dr. G. F. Murphy at gmurphy@rics.bwh.harvard.edu or Dr. C. G. Lian at cglian@partners.org
Frequent CCNE1 amplification in endometrial intraepithelial carcinoma and uterine serous carcinoma
Uterine serous carcinoma accounts for only 10 percent of all uterine epithelial cancers but is the leading cause of death among them. The pathogenesis of this aggressive neoplasm has been largely elusive, until recently, when comprehensive genome-wide analyses of uterine serous carcinoma were performed. The cancer-related gene CCNE1, encoding for cyclin E1, is frequently amplified in uterine serous carcinoma. The authors conducted a study in which they used FISH to determine CCNE1 copy number in uterine serous carcinoma and concurrent endometrial intraepithelial carcinoma, the noninvasive component of uterine serous carcinoma, and correlated the results with clinicopathological and molecular features. They found that 20 of 44 (45 percent) uterine serous carcinomas and 11 of 27 (41 percent) endometrial intraepithelial carcinomas showed CCNE1 amplification. Overall, the authors found high concordance in CCNE1 copy number in concurrent uterine serous carcinoma and endometrial intraepithelial carcinoma pairs (P=0.0003). No correlation was observed between CCNE1 copy number and clinicopathological features, as well as common mutations previously reported in uterine serous carcinoma. The authors concluded that this study confirms that amplification of CCNE1 is a frequent molecular genetic change in uterine serous carcinoma. Moreover, the identification of CCNE1 amplification in many endometrial intraepithelial carcinomas suggests that this genetic event occurs early in tumor progression.
Kuhn E, Bahadirli-Talbott A, Shih IM. Frequent CCNE1 amplification in endometrial intraepithelial carcinoma and uterine serous carcinoma. Mod Pathol. 2014;27:1014–1019.
Correspondence: Dr. E. Kuhn at elisabettakuhn@hotmail.it or Dr. Ie-Ming Shih at ishih@jhmi.edu
Tubal origin of ovarian endometriosis
Endometriosis is a puzzling and debilitating disease that affects millions of women worldwide. The ovary is the most common organ site involved by the disease. Despite various hypotheses about its cell of origin, uncertainty remains. On the basis of their clinicopathologic observations, the authors hypothesized that the fallopian tube may contribute the histogenesis of ovarian endometriosis. To examine if this hypothesis has scientific supporting evidence, they identified, through a gene differential assay study, a set of novel genes that are highly expressed in the normal fallopian tube or endometrium. FMO3 and DMBT1 were selected as the initial biomarkers to test the hypothesis. These biomarkers were then validated in ovarian sections with foci of endometriosis by comparing their expression levels in the fallopian tube and endometrium of the same patients using real-time PCR, Western blot, and immunohistochemistry analysis. FMO3 was highly expressed in the tubal epithelia and low in the paired endometrium. In contrast, DMBT1 was high in the endometrium but low in the fallopian tube. In 32 ovarian endometriosis cases analyzed by real-time PCR, 18 (56 percent) showed a high level of FMO3 and a low level of DMBT1 expression. However, 14 (44 percent) endometriosis cases showed a reversed expression pattern with these two markers. Similar results were generated using Western blot and immunohistochemistry. The findings suggest that approximately 60 percent of the cases of ovarian endometriosis in the study may have been derived from the fallopian tube, whereas about 40 percent of the cases may have been of endometrial origin. Fallopian tube epithelia may represent one of the tissue sources contributing to ovarian endometriosis. Such novel findings, which require confirmation, may have significant clinical impact in searching for alternative ways to prevent and treat endometriosis.
Yuan Z, Wang L, Wang Y, et al. Tubal origin of ovarian endometriosis. Mod Pathol. 2014;27:1154–1162.
Correspondence: Dr. B. Kong at kongbeihua@sdu.edu.cn or Dr. W. Zheng at zhengw@email.arizona.edu