***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Endometrial carcinoma ( EC ) is the most common malignancy of the female genital tract . Gene alterations and overexpression of various oncogenes are important in tumor development . The human HER 2 neu ( c-erbB-2 ) gene product is a transmembrane receptor with an intracellular tyrosine kinase that plays an important role in coordinating the endometrial growth factor receptor signaling network . The aim of this study was to investigate the expression of c-erbB-2 in endometrial cancer , to study its correlation to established prognostic parameters and estrogen receptor ( ER ) and progesterone receptor ( PR ) status . Methods Immunohistochemical ( IHC ) analyses of ER , PR and c-erbB-2 were performed in 72 EC cases . Results We detected a positive staining with c erbB 2 in 18.1 % of the cases and determined a statistically significant relation between c-erbB-2 and PR . We could not find a statistically significant relation between c-erbB-2 staining and ER . There was not a statistically significant difference between c-erbB-2 and histological grade . The highest level of c-erbB-2 was found in grade 2 cases . There was not any statistically significant relation between c-erbB-2 and menstrual status , myometrial invasion , lymph node status , stage and survival . Conclusions Although our study provides additional evidence of the potential prognostic role of c-erbB-2 , further prospect i ve and controlled studies are required to vali date their clinical usefulness OBJECTIVE To evaluate the part played by several parameters in the prognosis of patients with endometrial carcinoma . STUDY DESIGN Eighty imprint smears from fresh endometrial tumor specimens were studied immunocytochemically for the expression of p53 , bcl-2 and epidermal growth factor receptor . Also , the presence of estrogen receptor ( ER ) and progesterone receptor ( PR ) in the tumor tissue was measured . The data obtained were related to survival , and associations were sought between the parameters studied . RESULTS Strong associations were found between advanced stage , high grade , lymph node metastases at diagnosis , nonendometrioid histology and p53 expression with poor survival . Bcl-2 expression was associated with good five-year survival . ER expression was associated marginally with good five-year survival , but PR expression was not . A strong association was found between p53 and advanced disease , stage and lymph node metastases at diagnosis . An association between EGFR positivity and survival was not found . CONCLUSION p53 Expression of uterine tumors is an independent and strong indicator of poor prognosis . Even patients with stage I and II disease at surgery who have p53-positive tumors must be considered at high risk Prospect ively , the relationship between and rogen levels in the utero-ovarian circulation , aromatase activity in endometrial and body fat tissue , and the presence or absence of endometrioid endometrial cancer was studied in postmenopausal women . In 43 women with endometrioid endometrial cancer and 8 women with a benign gynecological condition , a hysterectomy with bilateral salpingo-oophorectomy was performed . Using tritium water-release assays , aromatase activities in endometrial and body fat tissue were determined and related to the steroid levels from the peripheral and the utero-ovarian venous circulation ( estradiol , and rostenedione , testosterone ) and to the presence or absence of endometrial cancer . Significant aromatase activity was found in both benign and malignant endometrial tissue sample s. Aromatase activity in sample s of endometrial tissue and in sample s of body fat did not correlate with steroid levels in peripheral or utero-ovarian venous blood . Aromatase activity in sample s of benign or malignant endometrium did not differ . Remarkably , in four women with mainly poorly differentiated endometrial cancer , very high aromatase activity was found in endometrial tissue . It is likely that multiple pathogenetic pathways exist that eventually lead to the formation of endometrioid endometrial cancer . The local availability of and rogens and the finding that aromatase activity is present in both endometrial cancer and benign endometrial tissue support the hypothesis that aromatase activity in the endometrium may play a role in malignant transformation by converting and rogens into mitogenic estrogens in the endometrial tissue The author presents a hypothesis that the complex of endocrine and metabolic disturbances arising long before the development of endometrial carcinoma determines the biological peculiarities of the tumor , its clinical course , and the prognosis of the disease . On the basis of a prospect i ve study of 366 patients with endometrial carcinoma , the author postulates that there are two different pathogenetic types of endometrial carcinoma . The first pathogenetic type of the disease arises in women with obesity , hyperlipidemia , and signs of hyperestrogenism : anovulatory uterine bleeding , infertility , late onset of the menopause , and hyperplasia of the stroma of the ovaries and endometrium . The second pathogenetic type of the disease arises in women who have no signs stated above or these signs are not clearly defined . The frequency of the first pathogenetic type in the studied group of women was 65 % , whereas the frequency of the second type was 35 % . The peculiarities outlined above which are characteristic of the first pathogenetic type of the disease determine the development of highly and moderately differentiated tumors ( 82.3 % G1 and G2 ) , superficial invasion of the myometrium ( 69.4 % ) , high sensitivity to progestogens ( 80.2 % ) , and favorable prognosis ( 85.6 % 5-year survival rate ) . In patients who have the second pathogenetic type of endometrial cancer when endocrine and metabolic disturbances are absent or occult , poorly differentiated tumors arise ( 62.5 % G3 ) , a tendency to deep invasion of tumor into the myometrium is observed ( 65.7 % ) ; high frequency of metastatic spread into the pelvic lymph nodes ( 27.8 % ) ; decrease of sensitivity to progestogens ( 42.5 % ) ; and doubtful prognosis ( 58.8 % 5-year survival rate ) are noted For patients with localized endometrial carcinoma at primary operation , there is a definite need for more specific prognostic parameters to select patients for adjuvant therapy . The purpose of this study was to evaluate the applicability and prognostic significance of markers for tumor cell proliferation ( S phase fraction and Ki-67 expression ) among endometrial carcinoma patients , relative to the information derived from established clinicopathological variables including DNA and receptor analyses . In a prospect i ve study of 115 patients treated for endometrial carcinoma , fresh tumor tissue was collected for assessment s of ploidy , S phase fraction and hormone receptor concentrations . Ki-67 expression was assessed immunohistochemically on sections from formalin-fixed and paraffin-embedded tumor specimens . These variables were examined together with traditional clinicopathological features in univariate and multivariate ( Cox proportional hazards regression model ) survival analyses . The median follow-up time for the survivors was 9 years ( range , 5 - 15 ) , with no patient lost due to insufficient follow-up information . The expression of Ki-67 was significantly associated with International Federation of Gynecology and Obstetrics ( FIGO ) stage ( P = 0.0004 ) , histological type ( P = 0.03 ) , and histological grade ( P = 0.0001 ) . S phase fraction was significantly associated with histological grade ( P = 0.02 ) , whereas the association with histological type was of borderline significance ( P = 0.07 ) . In univariate analyses , survival was significantly influenced by FIGO stage ( P < 0.0001 ) , histological type ( P = 0.0002 ) , histological grade ( P = 0.002 ) , ploidy ( P = 0.015 ) , S phase fraction ( P = 0.017 ) , progesterone receptor concentration ( P = 0.02 ) , and Ki-67 expression ( P < 0.0001 ) . In Cox regression analysis , FIGO stage ( hazard ratio , 11.7 ; 95 % confidence interval , 4.3 - 32.1 ) and Ki-67 ( hazard ratio , 8.7 ; 95 % confidence interval , 3.0 - 25.2 ) were the only variables with independent prognostic impact . When patients whose tumors were confined to the uterus were analyzed separately , Ki-67 was the only variable with an independent prognostic importance . Ki-67 expression was superior to S phase fraction both in applicability and prognostic value . FIGO stage and Ki-67 expression were the only variables with independent prognostic impact in Cox regression analysis . Ki-67 expression is assessed on the histological specimens taken routinely , with no separate sampling technique ; this should make it easy to use in a routine setting 
    Output:
    
Conclusions In patients with endometrial cancer , higher level of ER and PR predicted favorable survival , and increased level of HER2 was associated with poorer survival .
All of the three hormone receptors had prognostic value for survival