Use of keratin 34 beta E12 as an adjunct in the diagnosis of mammary intraepithelial neoplasia-ductal type - Benign and malignant intraductal proliferations

A variety of studies have investigated the role of low molecular weight (LM W) and high molecular weight (HMW) cytokeratin (CK expression in the normal breast and invasive breast carcinomas. A few studies with small numbers of cases have addressed this issue in intraductal proliferations of the breas t. This study investigates the expression of these CKs in a large series of ductal intraepithelial neoplasias of the breast. We examined 150 ductal ca rcinomas in situ (DCIS), 35 cases of intraductal hyperplasia (IDH), and 15 cases of atypical intraductal hyperplasia (AIDH). Immunohistochemistry was performed using monoclonal antibodies against CK-34 beta E12 (HMW CK), CK-8 , and CK-19 (LMW CK) on formalin-fixed, paraffin-embedded tissue. The inten sity (0, +1, +2, +3) and percentage of positive intraductal cells (0-100%) were multiplied to obtain a score from 0 to 300, The immunoprofiles of IDH, AIDH, and DCIS were categorized into four groups showing negative or low ( 0-60), moderate (61-100), high (101-200), and very high (201-300) scores. A ll cases of IDH showed an intensely positive reaction thigh to very high sc ores) fur CK-34 beta E12. In contrast, 90% of the DCIS showed a negative or only focal and weak reaction (negative or low score) for this antigen. The remaining 10% of DCIS showed a positive immunoreaction for CK-34 beta E12 with moderate to high scores. All cases of florid IDH and 96% of cases of D CIS expressed CK-8 intensely with high to very high scores. Although CK-19 was strongly expressed in 97% of cases of IDH thigh to very high scores), a very high score was also found in 80% of cases of DCIS that were positive for CK-19. Of the 15 AIDHs, 80% had a negative or only focal reaction (nega tive or low score) for CK-34 beta E12 and the remaining 20% had a moderate to high score for this antigen. Although CK-8 was strongly positive in 87% of cases of AIDH thigh to very high scores), only 53.5% of AIDHs showed int ense positivity for CK-19. The present study clearly shows that the immunop rofile of IDH is different from DCIS as far as HMW CK is concerned. Althoug h florid IDH is characterized by a diffuse and intense immunoreaction for H MW CK, the lack of or only weak positivity for HMW CK (CK-34 beta E12 is, i n most cases, a hallmark of ductal carcinoma in situ. The immunoprofile of AIDH is very similar to that of DCIS. The expression of CK-8 and CK-19 is n ot useful in separating the various categories of ductal intraepithelial pr oliferations of the breast. We recommend the use of CK-34 beta E12 as an ad junct in the diagnosis of a variety of problematic intraductal proliferatio ns of the breast.