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  Anatomic Abstracts

 

 

 

 

June 2010

Editors:
Michael Cibull, MD
Melissa Kesler, MD
Rouzan Karabakhtsian, MD
Megan Zhang, MD

PAX2 expression in low malignant potential ovarian tumors and low-grade ovarian serous carcinomas PAX2 expression in low malignant potential ovarian tumors and low-grade ovarian serous carcinomas

Ovarian tumors of low malignant potential and low-grade ovarian serous carcinomas are thought to represent different stages on a tumori-genic continuum and to develop along pathways distinct from high-grade ovarian serous carcinoma. The authors performed gene-expression profiling on three normal human ovarian surface epithelia samples and 10 low-grade and 10 high-grade ovarian serous carcinomas. Analysis of the gene-expression profiles of these samples identified 80 genes that were upregulated and 232 genes that were downregulated in low-grade ovarian serous carcinomas. PAX2 was found to be one of the most upregulated genes in low-grade ovarian serous carcinoma. The upregulation of PAX2 was validated by real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot, and immunohisto-chemical analyses. Real-time RT-PCR showed a statistically significant difference in PAX2 mRNA expression (expressed as fold change in com-parison to normal human ovarian surface epithelia) among ovarian tumors of low malignant potential (1837.38; n=8) and low-grade (183.12; n=17) and high-grade (3.72; n=23) carcinoma samples (P=.015). Western blot analysis revealed strong PAX2 expression in ovarian tumors of low malignant potential (67 percent; n=3) and low-grade carcinoma samples (50 percent; n=10) but no PAX2 protein expression in high-grade carci-nomas (zero; n=10). Using immunohistochemistry, tumors of low malignant potential (59 percent; n=17) and low-grade carcinoma (63 percent; n=16) samples expressed significantly stronger nuclear staining than high-grade ovarian carcinoma samples (9.1 percent; n=263). Furthermore, consistent with earlier immunohistochemical findings, PAX2 expression was noted in the epithelial cells of fallopian tubes but not in normal ovarian surface epithelial cells. These findings also support the two-tiered hypothesis that tumors of low malignant potential and low-grade ovarian serous carcinoma are on a continuum and are distinct from high-grade ovarian carcinomas. In addition, the absence of PAX2 expression in normal ovarian epithelia, but expression in fallopian tube fimbria and ciliated epithelial inclusions, would suggest the potential development of tumors of low malignant potential and of low-grade ovarian serous carcinomas from secondary Müllerian structures.

Tung CS, Mok SC, Tsang YT, et al. PAX2 expression in low malignant potential ovarian tumors and low-grade ovarian serous carcinomas. Mod Pathol. 2009;22(9):1243–1250.

Correspondence: Dr. K. K. Wong at kkwong@mdanderson.org
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Detecting metastases in sentinel lymph nodes Detecting metastases in sentinel lymph nodes

The National Surgical Adjuvant Breast and Bowel Project B-32 trial examined whether patients with initially negative sentinel lymph nodes who had occult metastases detected on deeper levels and cytokeratin immunohistochemistry stains were at risk for regional or distant metasta-ses. The experimental B-32 protocol was designed to detect metastases larger than 1.0 mm by examining sections approximately 0.5 and 1.0 mm deeper into the paraffin blocks (two levels; wide spacing). This pilot quality assurance study compared detection rates to a comprehensive pro-tocol designed to detect metastases larger than 0.2 mm (multilevel; narrow spacing). All nodes were sectioned grossly at close to 2.0 mm and all sections embedded in paraffin blocks. For clinical treatment, a single hematoxylin-and-eosin section was examined from each block. For 54 cases with one to five sentinel lymph nodes (SLNs) and all nodes negative, additional cytokeratin immunohistochemistry sections were evaluated every 0.18 mm through the block until no tissue remained. Twenty of 176 (11.4 percent) blocks harbored occult metastases. The B-32 protocol detected metastases in 11 blocks (6.3 percent), and nine additional blocks (5.1 percent) with metastases were detected on sections that would not have been evaluated (P=.002; correlated proportions). The median number of levels examined per block on the comprehensive protocol was 11 (range, 3–26); the B-32 protocol was fixed at two levels (median, 2; range, 1–2). The median thickness of node sections in the block was 2.1 mm (range, 0.7–4.8 mm) and the modal thickness was 2.3 mm. Although more comprehensive sectioning of SLNs detects additional micrometasta-ses, the data suggest diminishing returns and reduced cost-effectiveness for the comprehensive strategy.

Weaver DL, Le UP, Dupuis SL, et al. Metastasis detection in sentinel lymph nodes: comparison of a limited widely spaced (NSABP protocol B-32) and a comprehensive nar-rowly spaced paraffin block sectioning strategy. Am J Surg Pathol. 2009;33(11):1583–1589.

Correspondence: Dr. Donald Weaver at donald.weaver@vtmednet.org
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Origin of uterine leiomyosarcomas from associated leiomyoma and symplastic leiomyoma-like areas Origin of uterine leiomyosarcomas from associated leiomyoma and symplastic leiomyoma-like areas

It is uncertain whether uterine leiomyosarcoma arises de novo or in pre-existing leiomyoma. Leiomyoma-like areas can be seen associated with uterine leiomyosarcoma, raising the possibility of precursor lesions for uterine leiomyosarcoma. The authors conducted a study in which they examined cases of uterine leiomyosarcoma associated with leiomyoma-like areas at the histological, immunohistochemical, and DNA level to further evaluate if benign-looking leiomyoma-like and uterine leiomyosarcoma areas are related. They reviewed cases of uterine leiomyosar-coma observed at the New York University Medical Center from 1994 to 2007 for the presence of leiomyoma-like areas. Of the 26 cases of uter-ine leiomyosarcoma observed, 18 had an associated leiomyoma-like area (five cellular leiomyoma, four symplastic leiomyoma, four cellular and symplastic leiomyoma, and five usual type leiomyoma). Sixteen of the 18 cases were examined immunohistochemically for Ki-67, estrogen re-ceptor (ER), progesterone receptor (PR), and p53. Immunohistochemical profiles were as expected for leiomyoma-like areas (mean expression of p53, ER, PR, and Ki-67 at 0.3, 63, 75, and 0.6 percent, respectively), symplastic leiomyoma-like areas (mean expression of p53, ER, PR, and Ki-67 at 0.6, 85, 89, and 5.5 percent, respectively), and uterine leiomyosarcoma areas (mean expression of p53, ER, PR, and Ki-67 at 52, 38, 39, and 61 percent, respectively). In six cases, the leiomyoma-like and uterine leiomyosarcoma areas from each case were examined using high-density oligonucleotide array–comparative genomic hybridization to determine genetic aberrations in the two areas. Nearly all the genetic aberrations found in leiomyoma-like areas were also found in the corresponding uterine leiomyosarcoma areas. Furthermore, uterine leiomyosarcoma areas had additional genetic aberrations. The immunohistochemical profiles and genetic aberrations of the examined cases suggest that uterine leio-myosarcoma could arise from the pre-existing leiomyoma-like areas that often have a symplastic or cellular morphology.

Mittal KR, Chen F, Wei JJ, et al. Molecular and immunohistochemical evidence for the origin of uterine leiomyosarcomas from associated leiomyoma and symplastic leio-myoma-like areas. Mod Pathol. 2009;22(10):1303–1311.

Correspondence: Dr. K. R. Mittal at mittak01@med.nyu.edu
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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Melissa Kesler, MD, and Rouzan Karabakhtsian, MD, assistant professors of pathology and laboratory medicine, University of Kentucky College of Medicine; and Megan Zhang, MD, visiting fellow, Division of Dermatopathology, University of California, San Francisco.