Endometrial carcinoma is one of the most frequent malignant tumors in the uterus. Endometrial cancer has been known to originate from glandular proliferation accompanied by focal glandular crowding through simple, complex and atypical hyperplasia. But, molecular and tumor biological approaches have ...
Endometrial carcinoma is one of the most frequent malignant tumors in the uterus. Endometrial cancer has been known to originate from glandular proliferation accompanied by focal glandular crowding through simple, complex and atypical hyperplasia. But, molecular and tumor biological approaches have rarely been studied related to the multi-stage carcinogenesis mechanism or prognostic factors well established in gastrointestinal malignancies, Compared to uterine cervical cancer, endometrial cancer has some different tumor biological characteristics. In spite of marked improvements in its diagnosis and management considerable portions of patients still demonstrate poor prognosis. In general, the malignant tumor development results from various alterations in oncogeHes and tumor suppressor genes (TSG) accumulated during the carcinogenic process. Much efforts for elucidation of genetic events in endometrial carcinogenesis have recently been made. Microsatellite alteration such as loss of heterozygosity (LOH) has been reported as a novel mechanism of carcinogenesis and a useful prognostic factor in many malignant tumors. LOH is known to be related with allelic loss of various TSGs. The contritbution of microsatellite alteration of TSGs, however, is rarely studied to the development of endometrial carcinogenesis This study was conducted to investigate the possible microsatellite alterations associated with five major TSGs such as Fhit, p16, Rb, e-cadherin and p53 genes, and to correlate with clinico-pathological parameters. Thirty endometrial carcinomas treated by TAH and twenty endometrial hyperplasia obtained from curettage biopsy have been analyzed for the presence of LOH for chromosomes 3p14, 9p21, 13q14, 16q22 and 17p13, using microsatellite markers. DNA samples of endometrial cancer lesion and normal tissue were extracted from formalin-fixed paraffin-embedded archival tissues. LOH was examined at 10 microsatellite loci D3S1067, D3S1300, D9S104, D9S162, D13S118, D13S153, D16S421, D16S512, D17S796 and TP53. The CD44v6 protein expression was investigated by immunohistochemistry. Clinicopathological parameters such as age, stage, nodal metastasis and histological grade are compared with the LOH incidence on each chromosonle. There was no detectable LOH in normal endometrial tissue. LOH was observed in 26.7%, 60.0% and 100.0% in simple hyperplasia, atypical hyperplasia and endometrial carcinoma, respectively. LOH on chromosomes 3p14, 13q14 and 16q22 was found In 42.9%, 50.0% and 50.0% of cases in endometrial carcinoma. LOH on 9p21 and 17p13 was detected in both endometrial hypeprplasia and endometrial carcinoma. LOH on all chromosomes showed statistical difference between benign and malignant tumor. LOH on 3p14 was highly correlated with endometrial cancer of grade 1 (p=0.032), stage IA (p=0.002) without metastasis (p=0.010). LOH on 9p21 was detected more in grade 3 (p=0.026). LOH on 13q14 was well correlated with grade 1 (p=0.030) without metastasis (p=0.029). LOH detection rate on 16q22 and 17p13 was low in grade 2 and grade 1. CD44v6 protein expression was detected in 13.3%, 40.0% and 60.0% in simple hyperplasia, atypical hyperplasia and endometrial carcinoma, respectively. They were highly correlated with grade IA and grade IB malignancy (p=0.033). CD44v6 expression and microsatellite alterations on TSGs such as Fhit, p16, Rb, e-cadherin and p53 gone may contribute to the development of endometrial carcinoma as well as some subsets of endometrial hyperplasla. LOH of Fhit gene may be correlated with the stages higher than IB. LOH of Fhit and Rb genes may be correlated with Iymph nodal metastasis. Combined use of various LOH markers maybe helpful in deforming prognosis of endometrial tumor patients.
Endometrial carcinoma is one of the most frequent malignant tumors in the uterus. Endometrial cancer has been known to originate from glandular proliferation accompanied by focal glandular crowding through simple, complex and atypical hyperplasia. But, molecular and tumor biological approaches have rarely been studied related to the multi-stage carcinogenesis mechanism or prognostic factors well established in gastrointestinal malignancies, Compared to uterine cervical cancer, endometrial cancer has some different tumor biological characteristics. In spite of marked improvements in its diagnosis and management considerable portions of patients still demonstrate poor prognosis. In general, the malignant tumor development results from various alterations in oncogeHes and tumor suppressor genes (TSG) accumulated during the carcinogenic process. Much efforts for elucidation of genetic events in endometrial carcinogenesis have recently been made. Microsatellite alteration such as loss of heterozygosity (LOH) has been reported as a novel mechanism of carcinogenesis and a useful prognostic factor in many malignant tumors. LOH is known to be related with allelic loss of various TSGs. The contritbution of microsatellite alteration of TSGs, however, is rarely studied to the development of endometrial carcinogenesis This study was conducted to investigate the possible microsatellite alterations associated with five major TSGs such as Fhit, p16, Rb, e-cadherin and p53 genes, and to correlate with clinico-pathological parameters. Thirty endometrial carcinomas treated by TAH and twenty endometrial hyperplasia obtained from curettage biopsy have been analyzed for the presence of LOH for chromosomes 3p14, 9p21, 13q14, 16q22 and 17p13, using microsatellite markers. DNA samples of endometrial cancer lesion and normal tissue were extracted from formalin-fixed paraffin-embedded archival tissues. LOH was examined at 10 microsatellite loci D3S1067, D3S1300, D9S104, D9S162, D13S118, D13S153, D16S421, D16S512, D17S796 and TP53. The CD44v6 protein expression was investigated by immunohistochemistry. Clinicopathological parameters such as age, stage, nodal metastasis and histological grade are compared with the LOH incidence on each chromosonle. There was no detectable LOH in normal endometrial tissue. LOH was observed in 26.7%, 60.0% and 100.0% in simple hyperplasia, atypical hyperplasia and endometrial carcinoma, respectively. LOH on chromosomes 3p14, 13q14 and 16q22 was found In 42.9%, 50.0% and 50.0% of cases in endometrial carcinoma. LOH on 9p21 and 17p13 was detected in both endometrial hypeprplasia and endometrial carcinoma. LOH on all chromosomes showed statistical difference between benign and malignant tumor. LOH on 3p14 was highly correlated with endometrial cancer of grade 1 (p=0.032), stage IA (p=0.002) without metastasis (p=0.010). LOH on 9p21 was detected more in grade 3 (p=0.026). LOH on 13q14 was well correlated with grade 1 (p=0.030) without metastasis (p=0.029). LOH detection rate on 16q22 and 17p13 was low in grade 2 and grade 1. CD44v6 protein expression was detected in 13.3%, 40.0% and 60.0% in simple hyperplasia, atypical hyperplasia and endometrial carcinoma, respectively. They were highly correlated with grade IA and grade IB malignancy (p=0.033). CD44v6 expression and microsatellite alterations on TSGs such as Fhit, p16, Rb, e-cadherin and p53 gone may contribute to the development of endometrial carcinoma as well as some subsets of endometrial hyperplasla. LOH of Fhit gene may be correlated with the stages higher than IB. LOH of Fhit and Rb genes may be correlated with Iymph nodal metastasis. Combined use of various LOH markers maybe helpful in deforming prognosis of endometrial tumor patients.
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