Pathologic features of endometrial carcinoma associated with HNPCC

A comparison with sporadic endometrial carcinoma

Russell R. Broaddus, Henry T. Lynch, Lee May Chen, Molly S. Daniels, Peggy Conrad, Mark F. Munsell, Kristin G. White, Rajyalakshmi Luthra, Karen H. Lu

Research output: Contribution to journalArticle

200 Citations (Scopus)

Abstract

BACKGROUND. Endometrial carcinoma is a common malignancy in hereditary nonpolyposis colorectal carcinoma (HNPCC). Like colon carcinoma, endometrial carcinoma is diagnosed at an earlier age in women with HNPCC. In contrast to colon carcinoma, the pathologic features of endometrial carcinoma in HNPCC have not been studied in detail. It was the purpose of this study to pathologically characterize a series of HNPCC associated endometrial carcinomas. METHODS. Fifty women with HNPCC and endometrial carcinoma were analyzed from four different hereditary cancer registries. H&E stained slides and pathology reports were reviewed for clinically important pathologic features of endometrial carcinoma. These results were compared with those for two different groups of sporadic endometrial carcinoma - women younger than age 50 years (n = 42) and women of all ages with tumors demonstrating microsatellite instability (MSI-high) secondary to methylation of MLH1 (n = 26). RESULTS. Nearly one-fourth of HNPCC patients in this study had endometrial tumors with pathologic features that would require adjuvant therapy after hysterectomy. There was a trend toward the HNPCC patients having more nonendometrioid tumors; all of these patients were carriers of MSH2 mutations. Such nonendometrioid tumors were extremely rare in the MLH1 methylated group. A subset of MLH1 methylated sporadic tumors demonstrated a unique, 'undifferentiated' histology that was not observed in HNPCC or the young group. CONCLUSION. Data suggest a genotype-phenotype relation in which microsatellite instability resulting from MLH1 methylation is almost exclusively associated with classical or 'undifferentiated' endometrioid tumors, whereas microsatellite instability secondary to MSH2 mutation can result in a more variable histologic spectrum of endometrial carcinoma.

Original languageEnglish
Pages (from-to)87-94
Number of pages8
JournalCancer
Volume106
Issue number1
DOIs
StatePublished - Jan 1 2006

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Endometrial Neoplasms
Colorectal Neoplasms
Microsatellite Instability
Neoplasms
Methylation
Colon
Carcinoma
Mutation
Hysterectomy
Registries
Histology
Genotype
Pathology
Phenotype

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Broaddus, R. R., Lynch, H. T., Chen, L. M., Daniels, M. S., Conrad, P., Munsell, M. F., ... Lu, K. H. (2006). Pathologic features of endometrial carcinoma associated with HNPCC: A comparison with sporadic endometrial carcinoma. Cancer, 106(1), 87-94. https://doi.org/10.1002/cncr.21560

Pathologic features of endometrial carcinoma associated with HNPCC : A comparison with sporadic endometrial carcinoma. / Broaddus, Russell R.; Lynch, Henry T.; Chen, Lee May; Daniels, Molly S.; Conrad, Peggy; Munsell, Mark F.; White, Kristin G.; Luthra, Rajyalakshmi; Lu, Karen H.

In: Cancer, Vol. 106, No. 1, 01.01.2006, p. 87-94.

Research output: Contribution to journalArticle

Broaddus, RR, Lynch, HT, Chen, LM, Daniels, MS, Conrad, P, Munsell, MF, White, KG, Luthra, R & Lu, KH 2006, 'Pathologic features of endometrial carcinoma associated with HNPCC: A comparison with sporadic endometrial carcinoma', Cancer, vol. 106, no. 1, pp. 87-94. https://doi.org/10.1002/cncr.21560
Broaddus, Russell R. ; Lynch, Henry T. ; Chen, Lee May ; Daniels, Molly S. ; Conrad, Peggy ; Munsell, Mark F. ; White, Kristin G. ; Luthra, Rajyalakshmi ; Lu, Karen H. / Pathologic features of endometrial carcinoma associated with HNPCC : A comparison with sporadic endometrial carcinoma. In: Cancer. 2006 ; Vol. 106, No. 1. pp. 87-94.
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AU - Daniels, Molly S.

AU - Conrad, Peggy

AU - Munsell, Mark F.

AU - White, Kristin G.

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N2 - BACKGROUND. Endometrial carcinoma is a common malignancy in hereditary nonpolyposis colorectal carcinoma (HNPCC). Like colon carcinoma, endometrial carcinoma is diagnosed at an earlier age in women with HNPCC. In contrast to colon carcinoma, the pathologic features of endometrial carcinoma in HNPCC have not been studied in detail. It was the purpose of this study to pathologically characterize a series of HNPCC associated endometrial carcinomas. METHODS. Fifty women with HNPCC and endometrial carcinoma were analyzed from four different hereditary cancer registries. H&E stained slides and pathology reports were reviewed for clinically important pathologic features of endometrial carcinoma. These results were compared with those for two different groups of sporadic endometrial carcinoma - women younger than age 50 years (n = 42) and women of all ages with tumors demonstrating microsatellite instability (MSI-high) secondary to methylation of MLH1 (n = 26). RESULTS. Nearly one-fourth of HNPCC patients in this study had endometrial tumors with pathologic features that would require adjuvant therapy after hysterectomy. There was a trend toward the HNPCC patients having more nonendometrioid tumors; all of these patients were carriers of MSH2 mutations. Such nonendometrioid tumors were extremely rare in the MLH1 methylated group. A subset of MLH1 methylated sporadic tumors demonstrated a unique, 'undifferentiated' histology that was not observed in HNPCC or the young group. CONCLUSION. Data suggest a genotype-phenotype relation in which microsatellite instability resulting from MLH1 methylation is almost exclusively associated with classical or 'undifferentiated' endometrioid tumors, whereas microsatellite instability secondary to MSH2 mutation can result in a more variable histologic spectrum of endometrial carcinoma.

AB - BACKGROUND. Endometrial carcinoma is a common malignancy in hereditary nonpolyposis colorectal carcinoma (HNPCC). Like colon carcinoma, endometrial carcinoma is diagnosed at an earlier age in women with HNPCC. In contrast to colon carcinoma, the pathologic features of endometrial carcinoma in HNPCC have not been studied in detail. It was the purpose of this study to pathologically characterize a series of HNPCC associated endometrial carcinomas. METHODS. Fifty women with HNPCC and endometrial carcinoma were analyzed from four different hereditary cancer registries. H&E stained slides and pathology reports were reviewed for clinically important pathologic features of endometrial carcinoma. These results were compared with those for two different groups of sporadic endometrial carcinoma - women younger than age 50 years (n = 42) and women of all ages with tumors demonstrating microsatellite instability (MSI-high) secondary to methylation of MLH1 (n = 26). RESULTS. Nearly one-fourth of HNPCC patients in this study had endometrial tumors with pathologic features that would require adjuvant therapy after hysterectomy. There was a trend toward the HNPCC patients having more nonendometrioid tumors; all of these patients were carriers of MSH2 mutations. Such nonendometrioid tumors were extremely rare in the MLH1 methylated group. A subset of MLH1 methylated sporadic tumors demonstrated a unique, 'undifferentiated' histology that was not observed in HNPCC or the young group. CONCLUSION. Data suggest a genotype-phenotype relation in which microsatellite instability resulting from MLH1 methylation is almost exclusively associated with classical or 'undifferentiated' endometrioid tumors, whereas microsatellite instability secondary to MSH2 mutation can result in a more variable histologic spectrum of endometrial carcinoma.

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