Staining characterization by immunohistochemistry of tumor cancer antigen in patients with endometrial cancer

Objective: The aim of the present study was to evaluate the correlation between the pattern of cancer antigen (CA-125) expression by immunohistochemistry and pathologic parameters in endometrial carcinoma. Methods: Seventy-two cases of primary uterine carcinomas, 66 endometrioid carcinoma and six non-endometrioid, were analyzed by immunohistochemistry for CA-125 expression. Myometrial invasion was evaluated by assessing the percentage of myometrial thickness involved at the site of deepest tumor extension. Presence or absence of vascular invasion, cervical stromal invasion, lymph node metastasis, and ovarian metastasis from endometrial cancer was assessed. Tumor size was measured by the maximum diameter. Peritoneal washings were examined for the presence or absence of cancer cells. The extent and location of immunohistochemical staining for CA-125 was assessed according to the immunoreactive score (IRS) that evaluated the proportion of cells expressing CA-125 and the intensity of staining. Percentage of the cancer area stained in high-power fields was examined. Staining intensity was graded as 0 (negative), 1 (weak), 2 (modarate), and 3 (strong); percentage of positive cells examined was scored as 0 (negative), 1 (< 10%), 2 (11-50%), 3 (5 1-80%) and 4 (> 80%). The two scores were multiplied and the IRS (values from 0-12) was determined: 0 as negative, values 1-3 as weak, values 4,6 as positive, and multiplication values 8, 9, 12 as strongly positive. Results: Of the 72 patients, 66 (91.7%) had endometrioid carcinoma and six (8.3%) had non-endometrioid carcinoma. Of the seventy-two patients, 38 (52.7%) had surgical Stage I disease, 12 (16.7%) had Stage II, 16 (22.2%) had Stage III disease, and six (8.4%) had Stage IV disease. Ten (14.7%) of the 68 patients who underwent lymphadenectomy had positive nodes. Nine (12.5 %) of 72 patients had positive peritoneal cytologic findings. Forty-eight (66.7%) patients had deep myometrial invasion, 29 (40.3%) had lymphovascular invasion, 25 (34.7%) had cervical stromal involvement, and 12 (16.7%) had ovarian metastasis. Twenty-eight (38.9%) patients had grade 1, 25 (34.7%) had grade 2, and 19 (26.4%) had grade 3 disease. Fifty-nine (81.9%) patients had a tumor size greater than 2 cm. Negative staining was noted in ten (13.9%) tumors, weakly positive in 23 (31.9%), positive in 16 (22.3%) and strongly positive in 23 (31.9%). Grade 0 intensity was found in nine (12.5%) tumors, grade 1 in 16 (22.3%), grade 2 in 21 (29.16), and grade 3 in 26 (36.11). Negative percentage of positive cells examined was found in nine (12.5%) tumors, < 10% in 19 (26.38%), 11-50% in 18(25%), 51-80% in 13 (18.05%), > 80 in 13 (18.05%). We found that intensity, percentage of positive stained cells, and IRS correlated with deep myometrial invasion (p < 0.05). Conclusions: Intensity, percentage of positive stained cells for CA-125, and IRS can be used to determine the need for abdominal hysterectomy and lymphadenectomy for staging in endometrial cancer.

Endometrial carcinoma; CA-125; Immunohistochemistry

[1] Kabawat S.E., Bast R.C., Bahn A.K., Welch W.R., Knapp R.C., Colvin R.B.: “Tissue distribution of a coelemic epithelium-related antigen recognized by the monoclonal antibody OC 125”. Int. J. Gynecol. Pathol., 1983, 2, 275.

[2] Neunteufel W., Breitenecker G.: “CA-125 and CEA in the endometrial mucosa during the menstrual cycle, in atypical hyperplasia and endometrial carcinoma”. Cancer Lett., 1989, 48, 77.

[3] Podczaski E., Kaminski P., Zaino R.: “CA-125 and CA-19-9 immunolocalization in normal, hyperplastic and carcinomatous endometrium”. Cancer, 1993, 71, 2551.

[4] Mylonas I., Makovitzky J., Richter D.U., Jeschke U., Briese V., Friese K.: “Immunohistochemical expression of the tumour marker CA-125 in normal, hyperplastic and malignant endometrial tissue”. Anticancer Res., 2003, 23, 1075.

[5] Bischof P., Schindler A.M., Urner F., Mensi N., Herrmann W.L., Sizonenko P.C.: “Pregnancy-associated plasma protein: concentration in uterine fluid and immunohistochemical localization in the endometrium”. Br. J. Obstet. Gynecol., 1984, 91, 863.

[6] Zeimet A.G., Muller-Holzner E., Marth C., Daxenbichler G., Dapunt O.: “Tumor marker CA-125 in tissues of the female reproductive tract and in serum during the normal menstrual cycle”. Fertil. Steril., 1993, 59, 1028.

[7] Weintraub J., Bishof P., Tseng L., Redard M., Vassilakos P.: “CA-125 is an excretory product of human endometrial glands”. Biol. Reprod., 1990, 42, 721.

[8] News FIGO: “Corpus cancer staging”. Int. J. Gynecol. Obstet., 1989, 28, 189.

[9] Jhang H., Chaung L., Visintainer P., Ramaswamy G.: “CA-125 levels in the preoperative assessment of advanced-staged uterine cancer”. Am. J. Obstet. Gynecol., 2003, 188, 1195.

[10] Silverberg S.G., Kurman R.J., Nogales F.: “Tumours of the uterine corpus”. In: Tavassoli F.A., Devilee P. (eds.), World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon, IARC Press, 2003, 221.

[11] Remmele W., Schicketanz K.H.: “Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS)”. Pathol. Res. Pract., 1993, 189, 862.

[12] Fedele L., Vercellini P., Arcaini L., da Dalt MG., Candiani G.B.: “CA-125 in serum, peritoneal fluid, active lesions and endometrium of patients of endometriosis”. Am. J. Obstet. Gynecol., 1988, 158, 166.

[13] Berchuck A., Soisson A.P., Clarke-Pearson D.L., Soper J.T., Boyer C.M., Kinney R.B., McCarty K.S. Jr., Bast R.C. Jr.: “Immunohistochemical expression of CA-125 in endometrial adenocarcinoma: correlation of antigen expression with metastatic potential”., Cancer Res., 1989, 49, 2091.

[14] Nur S., Chuang L., Ramaswamy G.: “Immunohistochemical characterization of cancer antigen in uterine cancer”. Int. J. Gynecol. Cancer, 2006, 16, 1903.