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Abstract Summary and Conclusion A total number of 52 cases of endometrial lesions, benign and malignant, were studied histopathologically (for typing of the lesion, grading of the tumors, detection of mean apoptotic index in different lesions, and other histopathological changes in different grades) and inmmunohistochemically for localization of HIlT gene in malignant and premalignant lesions in relation to tumor behavior as histopathological type, tumor grade and any available data. The cases were selected to represent a spectrum of endometrial changes including proliferative phase (n=8), secretory phase (n=2); simple hyperplasia (n= 10), complex hyperplasia (n= 10), atypical hyperplasia (n=8); and various grades of endometrioid carcinoma, GI (n=9), Gil (n=8), and GIll (n=7). This study revealed that HIlT was strongly expressed in 100% of cases of proliferative, secretory phases of the menstrual cycle as well as simple and complex hyperplasia but reduced in 25% of cases of atypical hyperplasia. This may indicate that alteration of the FHIT gene is an early event in carcinogenesis of the endometrium. Concerning adenocarcinoma of the endometrium, 54.2% of cases revealed reduced pFHIT expression with significant progressive reduction with higher histological grade of the tumor. FHIT protein expression was markedly down regulated in adenocarcinoma of the endometrium when compared to normal and hyperplastic endometrium with a significant statistical difference (p<O.Ol). -150- summary and Conclusion The distribution of the marker was carefully examined to detect different immunohistochemical localizations for each lesion, From which, pFHIT expression was found to be helpful in differentiation between some cases of atypical endometrial hyperplasia and complex hyperplasia (pure apical stain in 50% of cases of atypical hyperplasia only); GIl adenocarcinoma from GI (by the appearance of nuclear together with cytoplasmic stain starting from GIl), and GIll (by appearance of pure nuclear stain in 28.6% of cases only in GIll) (p< 0.05). This study revealed the importance of pFHIT expression ill differentiation between some cases of atypical hyperplasia (reduced in 25% of cases) and complex hyperplasia. While, apoptotic index showed no significant difference between the two types of hyperplasia. In endometrioid carcinoma, it was found that higher grades was associated with higher MAl (P< 0.01), with significant correlation between FHIT expression and the apoptotic index (p<0.01). In the current study, we found that high grades of endometrioid carcinoma was associated with less desmoplastic reaction (P<0.05) which was significantly correlated with FHIT expression; and more vascular invasion (P<0.05) which was inversely correlated with FHIT expression. While, it was found that there was no significant correlation between the grade and heavy lymphocytic infiltration (p> 0.05) or tumor necrosis (p>0.05); both showed insignificant correlation with FHIT expression. -151- Summary and Conclusion It was concluded from this study that pFIllT expression could be helpful in differentiation of different endometrial lesions by its expression and localization. Also, FIllT abnormalities provide an opportunity for accumulating genetic mutation and evolution from a precursor lesion to invasive carcinoma. Further studies are recommended to study pFIllT expression in a larger number of cases to define its importance in endometrial adenocarcinoma and other types of endometrial carcinomas and sarcoma and to investigate its expression as a prognostic marker for treatment in endometrial carcinomas. -152- Summary and Conclusion |