Expression And Clinical Significance Of ER, PR, P53, Ki-67 And Survivin In Endometrial Carcinomas: A Clinical Analysis Of 124 Cases With Endometrial Carcinoma

Objective: Endometrial carcinoma (EC) is one of the most common malignancies in the female genital tract. The 5-year survival is 84% ,and 75% of EC present in early stage. But some cases, including some ones with early stage, have bad prognosis. Then how to choose these high risk patients and to make a good treatment plan, has been a hot spot of clinical research. The known clinicopathologic features have been the important prognosis factors, such as pathologic type, surgical pathologic stage, histologic classification. Recent studies found that some biological parameters, have the correlation with occuring, development and prognosis of carcinoma, such as steroid receptors, oncogenes, anti-oncogene and other transferring related genes. Our research selected five immunohistochemical factors, including estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67 and Survivin. By analyzing the correlation of the expression levels of ER, PR, p53, Ki-67, Survivin and the clinicopathologic features, to explore the relationship of their expressions with the ocurring and development of EC, and to judge their potential as the prognostic indicators.Methods: We collected clinicalpathological and immunohistochemical factors data of 124 cases with EC, surgically treated at HeBei Medical University from April 2008 to March 2009. The relationship of clinicopathologic features with the expression levels of ER, PR, p53, Ki-67 and Survivin were analyzed through seven aspects, including pathologic type, histologic type, surgical pathologic stage, histologic grade, myometrial invasion, lymph node metastasis and lymph vascular space involvement. SPSS12.0 was used for statistical analysis.Results:1 Clinical data1.1 AgeThe average age was 53.4 years with a range from 28 to 75 years. The peak age range of EC was from 50 to 59, whose constituent ratio was 53.2%. Age was not related to histological type, pathologic stage and histologic grade of EC (P>0.05).1.2 Menstruation conditionThe average menarche age was 15.8 years.The incidence of pre-menopause was 56.5%, and that of post-menopause was 43.5%. The average menopause age was 49.37. Menopause age was not related to histological type, pathologic stage and histologic grade of EC (P>0.05).1.3 Procreation conditionThe average gravidity was 2.85, and average parity was 2.06. There was 15 cases (12.1%) unprocreation. And the procreation condition had no correlation with histological type, pathologic stage and histologic grade (P>0.05).1.4 Body weight, Body stature and Body Mass Index (BMI)The average body weight was 65.81kg. The average stature was 1.59m. The average BMI was 25.81. And 73 patients (58.9%) was overweight, BMI>25.0.1.5 Clinical manifestationVaginal irregular bleeding was the major clinical symptom, it took place in 83.0% cases. Heart disease was observed in 8 cases (6.5%), while 32 (25.8%) and 10 (8.1%) cases presented with high blood pressure and diabetes. The average levels of blood glucose, cholesterin and triglyceride were 6.53 mmol/L, 5.90 mmol/L and 1.46 mmol/L. And the average age of patients with high level of blood glucose, cholesterin and triglyceride was older than the people with normal vaule.1.6 Serum CA125In the tested 118 cases, the average serum CA125 was 38.56 u/ml. 32 cases (27.1%) had higher levels than 35 u/ml. If we looked 35 u/ml and 20 u/ml as the line of demarcation from normal value respectivelly, then the level of CA125 had a correlation with pathologic stage (P<0.05),but it had no correlation with histological type (P>0.05).1.7 Operation mode107 cases(86.3%) underwent hysterectomy with different range, bilateral salpingo-oophorectomy, and lymph node dissection. 17 cases underwent no lymph node dissection.2 Pathologic data①Pathologic type:113 of 124 patients(91.1%) were typeⅠEC, and 11(9.9%) were typeⅡEC.②Histologic type:105 of 124 patients (84.7%) were endometrioid carcinoma, and 19 (15.3%) were non-endometrioid carcinoma.③Surgical pathologic stage:According to the International Federation of Gynecology and Obstetrics (FIGO) classification (1988), 67 of the 124 patients(54.0%) were stageⅠ, 33(26.6%) were stageⅡ, 20(16.1%) were stageⅢ, and 4(3.3%) were stageⅣ.④Histologic grade: 30 of the 105 patients (28.6%) with endometrioid carcinoma were gradeⅠ, 67(63.8%) were gradeⅡ, 30(28.6%) were gradeⅢ. 19 cases with non-endometrial carcinoma weren't classified by histologic grade.⑤Myometrial invasion: Of the 124 cases, 23(18.5%) showed invasion of more than 1/2 of the depth, and the remaining 101 cases (81.5%) showed no myometrial invasion or invasion with depth of 1/2 or less in the myometrium.⑥Lymph node metastasis: Lymph node metastasis was present in 11 (8.9%) of 124 cases, and the remaining 131 presented no lymph node metastasis.⑦Lymph vascular space involvement:11 of 124 cases(8.9%) presented lymph vascular space involvement, and the remaining 113 didn't present.3 Immunohistochemical dataImmunopositivity for ER, PR and p53 was observed in 97 (78.2%), 101 (81.5%) and 83 of all the 124 (66.9%)carcinoma cases, respectively. 99 of 105 cases (94.3%) were positive for Survivin. And 93(95.9%) of 97 cases were positive for Ki-67. 4 The relationship of the expression levels of ER, PR, p53, Ki-67 and Survivin with clinicopathologic features, including pathologic type,histologic type, surgical pathologic stage,histologic grade, myometrial invasion, lymph node metastasis and lymph vascular space involvement.4.1 The positive and overpositive expression rate of ER was higher in carcinomas of type I than in type II. The positive rate of PR was higher in type I cancinoma, no myometrial invasion or invasion with depth of 1/2 or less in the myometrium and no lymph node metastasis. The overpositive rate for PR was higher in type I carcinoma, early stages (I+II) and no myometrial invasion or invasion with depth of 1/2 or less in the myometrium. And all of the differences were statistically significant, P<0.05.4.2 The overpositive rate of p53 was lower in type I carcinoma, early stages (I+II) and no myometrial invasion or invasion with depth of 1/2 or less in the myometrium. The differences were statistically significant, P<0.05. The positive rate of p53 was not related to any clinicopathologic features.4.3 The overpositive rate for Ki-67 was lower in early stages (I+II),low histologic grade(grade I) and no myometrial invasion or invasion with depth of 1/2 or less in the myometrium. The differences were statistically significant, P<0.05. The positive rate for Ki-67 was not related to any clinicopathologic features. 4.4 The overpositive rate of Survivin was lower in no lymph vascular space involvement and no myometrial invasion or invasion with depth of 1/2 or less in the myometrium. The differences were statistically significant, P<0.05. The positive rate for Survivin was not related to any clinicopathologic features.5 The correlation among ER, PR, p53, Ki-67 and SurvivinPositive correlation between ER and PR expression was found (r=0.619,P<0.05). PR expression was negatively correlated with Ki-67 ( r=-0.208,P<0.05). And p53 expression was positively correlated with Survivin ( r=0.270,P<0.05). Other immunohistochemical factors had no significant correlations with each other.There were 33 cases with ER negative and/or PR negative. And the rate of late stage ,deep myometrial invasion with overpositive expression for Ki-67 in the 33cases was 47.1%,35.3%.The rate of proceed lymph vascular space involvement with overpositive expression for p53 in the 33cases was 50.0%.But there had no significant statistics disparity,P>0.05.Conclusion:1 In the high risk factors of EC, age and menopause age have no correlation with histologic type, pathologic stage, and histologic grade. Unprocreation patients have poor histologic grade,but had no correlation with histologic type and pathologic stage.2 Patients with high serum CA125 level have advanced pathologic stage,and it can be used as a good prognosis predictor.3 Patients with high positive and overpositive expression rate of ER and PR have better clinicopathologic features, and PR have a closer correlation with clinicopathologic features than ER. Patients with high positive and overpositive expression rate of p53, Ki-67 and Survivin have poorer clinicopathologic features, and the overpositive expression rate have closer correlation with clinicopathologic features than positive rate. ER. ER, PR,p53 have closer correlation with pathologic type.4 ER expression is positively correlated with PR. PR expression is negatively correlated with Ki-67. And p53 expressin was positively correlated with Survivin. Other immunohistochemical factors have no significant correlations with each other. ER, PR, p53, Ki-67 maybe a good immunohistochemical combination ,as a valuable prognosis predictor.