OBJECTIVETo study the value of immunocytochemical study for cyclin D1, c-erbB-2, Ki-67, p21(CIP1/WAF1) and 34betaE12 in fine needle aspiration cytology (FNAC) diagnosis of mammary lesions.

METHODSOne hundred and thirty-five cases of breast diseases, all with FNAC performed and follow-up histologic correlation available, were enrolled into the study. These included 43 cases of benign non-proliferative diseases, 45 cases of benign proliferative diseases and 47 cases of mammary carcinoma. Immunostaining for cyclin D1, c-erbB-2, Ki-67, p21(CIP1/WAF1) and 34betaE12 was carried out on FNAC smears and paraffin sections of the corresponding biopsy specimens. The statistical significance was analyzed using SPSS11.5 software.

RESULTSNo statistically significant difference was observed in the expression of cyclin D1, c-erbB-2, Ki-67, p21(CIP1/WAF1) and 34betaE12 within the groups of benign non-proliferative and benign proliferative breast diseases. On the other hand, a significant difference in immunostaining results was found between benign breast lesions and mammary carcinoma (P < 0.001). A panel of cyclin D1, 34betaE12 and c-erbB-2 immunostaining is highly sensitive and specific in confirming the diagnosis of mammary carcinoma in FNAC samples. A positive reaction for cyclin D1 and c-erbB-2, when coupled with a negative reaction for 34betaE12, showed to be the most reliable supportive evidence for the malignant cytologic diagnosis. When taking the results of either cyclin D1 or 34betaE12 immunostaining into consideration, the sensitivity and specificity for diagnosing carcinoma was 95.7% and 94.3% respectively. On the other hand, when any of the three immunostains suggested carcinoma, the diagnostic sensitivity and specificity became 97.9% and 92.0% respectively. If the immunostaining results of any two of the three markers suggested carcinoma, the diagnostic sensitivity and specificity became 72.3% and 100% respectively. Within the carcinoma group, the degree of expression of cyclin D1, p21(CIP1/WAF1) and 34betaE12 showed little difference amongst different cytologic grades (according to Robinson cytologic grading system). There were however differences in expression of c-erbB-2 and Ki-67. Highest expression rate was observed in grade 3 carcinoma, while lowest expression rate was observed in grade 1 carcinoma (only in 40.0% and 33.3% of cases respectively). Whenever either cyclin D1 positivity or 34betaE12 negativity was demonstrated, the diagnostic accuracy for grade 1 and grade 2 carcinoma was 93.3% and 96.2 % respectively.

CONCLUSIONSImmunocytochemical study using a panel of antibodies for cyclin D1, c-erbB-2, and 34betaE12 has significant diagnostic value in distinguishing between benign breast diseases and mammary carcinoma in FNAC samples. Cyclin D1 and 34betaE12 are especially useful in confirming the cytologic diagnosis of low-grade cancer.