免疫组织化学标记物在乳腺细针吸取细胞学鉴别诊断中的意义

Role of immunocytochemistry in fine needle aspiration cytology diagnosis of mammary lesions of breast

目的探讨免疫标记物对鉴别乳腺细针吸取细胞学(FNAC)良性病变和癌的意义。方法收集135例有随访资料、活检和组织病理学诊断对照的乳腺FNAC资料:良性病变88例,包括非增生性病变43例和增生性病变45例;乳腺癌47例,对其FNAC涂片和相应的石蜡切片作细胞周期蛋白(cyclin)D1、c-erbB-2、Ki-67、p21CIP1/WAF1(简称p21)和34βE12的免疫组织化学APAAP和ABC法检测。利用SPSS11·5软件进行分析。结果(1)以上各标记物在良性非增生性和增生性病变中的标记差异无统计学意义。(2)以上各标记物在良、恶性病变中的标记差异均有统计学意义(P<0·001)。多因素的logistic回归分析显示最有意义的组合标记物为cyclinD1(P<0·001)、34βE12(P<0·001)和c-erbB-2(P=0·003).cyclinD1、c-erbB-2阳性和34βE12阴性提示为癌,其组合诊断的敏感性和特异性最高。组合标记物共同判断,cyclinD1和34βE12任一判断为癌,诊断的敏感性和特异性分别为95·7%和94·3%;这三个标记物任一判断为癌,诊断的敏感性进一步上升至97·9%,特异性下降至92·0%;这三个标记物任两个共同判断为癌,诊断的敏感性为72·3%,特异性为100·0%。(3)在癌组中,根据Robinson细胞学分级把癌分为3级,cyclinD1、34βE12和p21在各级癌中的表达差异不大,而c-erbB-2和Ki-67在1级癌的阳性表达率最低,仅为40·0%和33·3%,在3级癌中阳性表达率最高。组合cyclinD1和34βE12,cyclinD1和34βE12,任一判断为癌,1级和2级癌的检出率为93·3%和96·2%。结论所检测的免疫标记物对良、恶性病变的鉴别诊断价值较大,组合cyclinD1、34βE12和c-erbB-2可最有效地提高癌的诊断敏感性和特异性。对鉴别分化好的乳腺癌和乳腺良性病变,最有效的组合为cyclinD1和34βE12。

Objective To study the value of immunocytochemical study for cyclin D1, c-erbB-2, Ki-67, p21^CIP1/WAF1 and 34βE12 in fine needle aspiration cytology （FNAC） diagnosis of mammary lesions. Methods One 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 nonproliferative 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 34βE12 was carried out on FNAC smears and paraffin sections of the corresponding biopsy specimens. The statistical significance was analyzed using SPSS11.5 software. Resets No statistically significant difference was observed in the expression of cyclin D1, c-erbB-2, Ki-67, p21^CIP1/WAF1 and 34βE12 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, 34βE12 and c-erbB-2 iminunostaining 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 34βE12, showed to be the most reliable supportive evidence for the malignant cytologic diagnosis. When taking the results of either cyclin D1 or 34βE12 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 34βE12 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 34βE12 negativity was demonstrated, the diagnostic accuracy for grade 1 and grade 2 carcinoma was 93.3% and 96. 2 % respectively. Conclusions Immunocytochemical study using a panel of antibodies for cyclin D1, c-erbB-2, and 34βE12 has significant diagnostic value in distinguishing between benign breast diseases and mammary carcinoma in FNAC samples. Cyclin D1 and 34βE12 are especially useful in confirming the cytologic diagnosis of low-grade cancer.