C-erbB-2 protein overexpression and c-erbB-2 gene amplification are frequently associated with a more aggresive and chemoresistant disease in cancer patients . C-erbB-2 is reported in 9-60% of the ECs . According to the results reported by Brys et al. the erbB-1 and erbB-2 mRNA expression level was significantly higher in malignant human endometrium compared to benign tissue. Moreover, a significant correlation between erbB-1 overexpression and tumor differentiation was observed (p < 0.001). However, protein expression did not correlate with any known prognostic variables .
Kohlberger et al. found 21% HER-2/neu oncoprotein expression and according to their study, clinical stage, histologic stage, histologic grade and depth of invasion did not correlate with c-erbB-2 oncoprotein expression . Therefore c-erbB-2 oncoprotein was observed in all clinical stages and it did not seem to be a late event in the natural history of EC. They also reported that c-erbB-2 oncoprotein expression was associated with poor overall survival (long-rank P-value 0.04) . Khalifa et al. reported that c-erbB-2 overexpression was significantly associated with depth of myometrial invasion . Coronado et al. found that prognostic value of the c-erbB-2 overexpression was higher in early stages than in advanced stages of disease. The authors commented that this might have been related to the higher levels of overexpression found in serous and G3 cancers .
We observed 18.1% positive staining with c-erbB-2 in our study; and there wasn't any expressive relation with c-erbB-2 and respectively menstrual status, age or depth of myometrial invasion. In our research, even though we determined approximately the same ratio of c-erbB-2 positivity in G1 and G3 tumors, we found out that the ratio of c-erbB-2 positivity was relatively high in G2 tumors. C-erbB-2 staining and grade did not show a statistically significant relation (p > 0.05). Most of the cases were in G2 and the statistical results might be related with the number of G2 cases and the insufficient number of G3 cases. We were able to make "staging" for 34 of the cases and most of them were at stage I. In our study, cerbB-2 positivity was determined in stage I and stage III tumors. There was only one case in stage II and there was not any c-erbB-2 expression. Even though we determined a relatively high proportion of c-erbB-2 expression in stage III tumors, there was not any statistically significant correlation because of the insufficient number of stage III cases.
In the study by Grushko et al. HER-2 gene amplification was detected in 44%. There was a significant association between the grade and HER-2 amplification among nonserous tumors. Neither overexpression nor amplification predicted overall survival after adjusting for treatment and performance status . Backe et al. also showed that immunohistochemically detected expression of c-erbB-2 was not a clinical prognostic factor in endometrial cancer .
In our study there was not a statistically significant relation between survival and c-erb-B-2. This result might be due to the insufficient number of followed-up patients and the short time period.
There are studies revealing that c-erbB-2 is a poor prognostic factor or it has no relation with prognosis. Because of that the c-erbB-2 immunstaining is difficult to use as a predictor for prognosis . It is well-known that anti c-erbB-2 antibodies have very variable sensitivity in formalin-fixed, paraffin-embedded tissue, and that other technical issues are also critical . The variability in c-erbB-2 immunostaining results in the literature is probably related both to a different mix of patients in different series, and the wide variety of antibodies and staining conditions used. However the number of cases with c-erbB-2 overexpression is small, in both our series and in the other series in the literature, limited the precision of the results.
It is well known that cytosolic ERs and PRs can be identified in EC and a correlation between the contents of ER and PR within individual lesions has been demonstrated. Well differentiated tumors are more likely to be ER and PR positive than poorly differentiated neoplasms. So, the presence of ER and PR in EC is suggested to be inversely proportional to the nuclear grade and FIGO stage of the lesion . In a study, ER and PR expression in EC was significantly associated with both well-differatiated and early-stage ECs which were positive for both ER and PR. (19). In the study by Bigsby et al. c-erbB-2 oncogene protein, epidermal growth factor receptor, ER, and PR were examined immunohistochemically in specimens of normal and neoplastic endometrium. There was an inverse relationship between overexpression of c-erbB-2 and PR in EC. On the other hand, the overexpression of c-erbB-2 in EC did not seem to be related to the loss of other differentiated characteristics .
Berchuck et al. in their study reported that high expression of c-erbB-2 was found in 27% of patients with metastatic disease compared with 4% of patients with disease confined to the uterus (p < 0.005). High cerbB-2 expression also was associated with absence of ER (p < 0.005) and with increased mortality from cancer . Benevolo et al. reported that c-erbB-2 expression also influenced the patient outcome in the group with tumors lacking PRs (p = 0.004). In multivariate analysis PRs and c-erbB-2 overexpression emerged as independent prognostic factors .
In our study, in low grade tumors the number of ER and PR positive cases were relatively high. There was a statistically significant relation between PR and the grade. PR expression ratio decreased in high grade tumors. C-erbB-2 staining and ER did not show a statistically significant relation (p > 0.05). However, it is noteworthy that, in ER negative cases, c-erbB-2 expression was high. We found a statistically significant relation between c-erbB-2 and PR (p < 0.05). There was an inverse relationship between overexpression of c-erbB-2 and PR in EC. In PR negative cases, expression of cerbB-2 was statistically significantly high. On the other hand; there was not any statistically significant relation between ER-stage-survival and PR-stage-survival. Even though we couldn't find any relation between these variables, we thought that absence of PR might be related to the worse clinical process depending on literature. Moreover, the absence of PR and c-erbB-2 expression in EC, which is known as endocrine related neoplasm, could be a reliable parameter in the selection of specific hormonal treatment models.