TY - JOUR
T1 - Clear cell carcinoma of the endometrium is characterized by a distinctive profile of p53, Ki-67, estrogen, and progesterone receptor expression
AU - Lax, S. F.
AU - Pizer, E. S.
AU - Ronnett, B. M.
AU - Kurman, R. J.
N1 - Funding Information:
This study was designed to analyze certain clinicopathological features and the profile of p53, Ki-67, estrogen (ER), and progesterone (PR) receptor expression of clear cell carcinoma of the endome-Ifium and to determine whether the pathogenesis of clear cell carcinomac an be accommodated by a dualistic model of endometrial carcinogenesis. In this model, endometrioid carcinoma develops from endometrial hyperplasia under unopposed estrogenic stimulation,a nd serous carcinoma develops in atrophic endometrium from a putativep recursor lesion designated endometrial intraepithelial carcb n0ma (EIC). Twenty-one clear cell carcinomas of the endometrium were analyzed and compared with 77 endometrioid carcinomas of all grades and 30 serous carcinomas. Clear cell carcinomas showed a distinctivei mmunoprofile characterized by immunonegativity for ER and PR, low immunoreactivity for p53, and a high Ki-67 proliferation index.E R, PR, and Ki-67 expression were similar to serous carcinoma, bat p53 expression was significantly lower in clear cell carcinoma (P < .05). ER and PR expression were significantly lower, and the gi-67 proliferation index was significantly higher in clear cell carci-ngmac ompared with endometrioid carcinomas (P < .05). p53 expression tended to be higher in clear cell carcinoma compared with end0me~oid carcinoma, but the difference was not statistically significant. In contrast to endometrioid carcinoma, dear cell carci-nomaw as rarely associated with endometrial hyperplasia and serous carcinomaw as not. Subdividing clear cell carcinoma morphologically In 1983, Bokhman 1 proposed dividing endometrial carcinoma into two broad categories that reflected two different pathogenetic pathways. The categories were based mainly on clinical features and were not correlated with specific histopathologic cell types. One pathway was associated with low-grade tumors and was related to estrogenic stimulation (type I), and the other pathway was associated with high-grade tumors and unrelated to estrogenic stimulation (type II). More recently, Sherman et at 2 expanded this concept to include histopathological and immunohistochemical findings for this classification. In their model, endome-tfi0id carcinoma was the archetypical type I carcinoma developing from atypical hyperplasia as a result of tm0pposed estrogenic stimulation, and serous carci- From the Departments of Pathology and Gynecology and Obstet-tics,D ivisiono f Gynecological Pathology, The Johns Hopkins Medical Institutions,B altimore, MD. Accepted for publication September 3, 1997. S.E Lax is a recipient of an Erwin Schroedinger scholarship of theA usnian Science Foundation (FWF). Address correspondence and reprint requests to Robert J. Kur-man, MD, Department of Pathology, The Johns Hopkins Medical Institutions,P athology 711,600 North Wolfe St, Baltimore MD 21287. Copyright ~ 1998 by W.B. Sannders Company 0046-8177/98/2906-000258.00/0 into one that resembled serous carcinoma (dear cell carcinoma with serous features) and another that did not (typical clear cell carcinoma) showed that clear cell carcinoma with serous features had a higher Ki-67 proliferation index than typical clear cell carcinoma, although expression of ER, PR, and p53 were similar. Clear cell carcinoma with serous features was associated with EIC in 50% and was not associated with endometrial hyperplasia. In contrast, typical clear cell carcinoma was associated with endometrial hyperplasia in 40% and was not associated with EIC. In summary, this studyprovides evidence that clear cell carcinoma Of the endometrinm, like serous carcinoma, is estrogen independent and shows a high Ki-67 proliferation index. In contrast to serous carcinoma, strong p53 expression occurred less frequently in clear cell carcinoma and predominantly in clear cell carcinoma with serous features. The findings suggest that the molecular events that underlie the development of clear cell carcinoma differ from those of endometrioid and serous carcinoma. HUM PATHOL 29:551-558. Copyright © 1998 by W.B. Saunders Company Key words:d ear cell carcinoma, endometrium, immunohistochemistry, endometrial carcinoma, endometrial carcinogenesis. Abbreviations: EIC, endometrial intraepithelial carcinoma; ER, estrogen receptor; PR, progesterone receptor; FIGO, International Federation of Gynecology and Obstetrics.
PY - 1998
Y1 - 1998
N2 - This study was designed to analyze certain clinicopathological features and the profile of p53, Ki-67, estrogen (ER), and progesterone (PR) receptor expression of clear cell carcinoma of the endometrium and to determine whether the pathogenesis of clear cell carcinoma can be accommodated by a dualistic model of endometrial carcinogenesis. In this model, endometrioid carcinoma develops from endometrial hyperplasia under unopposed estrogenic stimulation, and serous carcinoma develops in atrophic endometrium from a putative precursor lesion designated endometrial intraepithelial carcinoma (EIC). Twenty-one clear cell carcinomas of the endometrium were analyzed and compared with 77 endometrioid carcinomas of all grades and 30 serous carcinomas. Clear cell carcinomas showed a distinctive immunoprofile characterized by immunonegativity for ER and PR, low immunoreactivity for p53, and a high Ki-67 proliferation index. ER, PR, and Ki-67 expression were similar to serous carcinoma, but p53 expression was significantly lower in clear cell carcinoma (P < .05). ER and PR expression were significantly lower, and the Ki-67 proliferation index was significantly higher in clear cell carcinoma compared with endometrioid carcinomas (P < .05). p53 expression tended to be higher in clear cell carcinoma compared with endometrioid carcinoma, but the difference was not statistically significant. In contrast to endometrioid carcinoma, clear cell carcinoma was rarely associated with endometrial hyperplasia and serous carcinoma was not. Subdividing clear cell carcinoma morphologically into one that resembled serous carcinoma (clear cell carcinoma with serous features) and another that did not (typical clear cell carcinoma) showed that clear cell carcinoma with serous features had a higher Ki-67 proliferation index than typical clear cell carcinoma, although expression of ER, PR, and p53 were similar. Clear cell carcinoma with serous features was associated with EIC in 50% and was not associated with endometrial hyperplasia. In contrast, typical clear cell carcinoma was associated with endometrial hyperplasia in 40% and was not associated with EIC. In summary, this study provides evidence that clear cell carcinoma of the endometrium, like serous carcinoma, is estrogen independent and shows a high Ki-67 proliferation index. In contrast to serous carcinoma, strong p53 expression occurred less frequently in clear cell carcinoma and predominantly in clear cell carcinoma with serous features. The findings suggest that the molecular events that underlie the development of clear cell carcinoma differ from those of endometrioid and serous carcinoma.
AB - This study was designed to analyze certain clinicopathological features and the profile of p53, Ki-67, estrogen (ER), and progesterone (PR) receptor expression of clear cell carcinoma of the endometrium and to determine whether the pathogenesis of clear cell carcinoma can be accommodated by a dualistic model of endometrial carcinogenesis. In this model, endometrioid carcinoma develops from endometrial hyperplasia under unopposed estrogenic stimulation, and serous carcinoma develops in atrophic endometrium from a putative precursor lesion designated endometrial intraepithelial carcinoma (EIC). Twenty-one clear cell carcinomas of the endometrium were analyzed and compared with 77 endometrioid carcinomas of all grades and 30 serous carcinomas. Clear cell carcinomas showed a distinctive immunoprofile characterized by immunonegativity for ER and PR, low immunoreactivity for p53, and a high Ki-67 proliferation index. ER, PR, and Ki-67 expression were similar to serous carcinoma, but p53 expression was significantly lower in clear cell carcinoma (P < .05). ER and PR expression were significantly lower, and the Ki-67 proliferation index was significantly higher in clear cell carcinoma compared with endometrioid carcinomas (P < .05). p53 expression tended to be higher in clear cell carcinoma compared with endometrioid carcinoma, but the difference was not statistically significant. In contrast to endometrioid carcinoma, clear cell carcinoma was rarely associated with endometrial hyperplasia and serous carcinoma was not. Subdividing clear cell carcinoma morphologically into one that resembled serous carcinoma (clear cell carcinoma with serous features) and another that did not (typical clear cell carcinoma) showed that clear cell carcinoma with serous features had a higher Ki-67 proliferation index than typical clear cell carcinoma, although expression of ER, PR, and p53 were similar. Clear cell carcinoma with serous features was associated with EIC in 50% and was not associated with endometrial hyperplasia. In contrast, typical clear cell carcinoma was associated with endometrial hyperplasia in 40% and was not associated with EIC. In summary, this study provides evidence that clear cell carcinoma of the endometrium, like serous carcinoma, is estrogen independent and shows a high Ki-67 proliferation index. In contrast to serous carcinoma, strong p53 expression occurred less frequently in clear cell carcinoma and predominantly in clear cell carcinoma with serous features. The findings suggest that the molecular events that underlie the development of clear cell carcinoma differ from those of endometrioid and serous carcinoma.
KW - Clear cell carcinoma
KW - Endometrial carcinogenesis
KW - Endometrial carcinoma
KW - Endometrium
KW - Immunohistochemistry
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U2 - 10.1016/S0046-8177(98)80002-6
DO - 10.1016/S0046-8177(98)80002-6
M3 - Article
C2 - 9635673
AN - SCOPUS:0031746796
SN - 0046-8177
VL - 29
SP - 551
EP - 558
JO - Human pathology
JF - Human pathology
IS - 6
ER -