Cytokeratins in Papillary Lesions of the Breast

Abstract

We studied 50 papillary lesions (25 papillomas and 25 papillary ductal carcinomas in situ, DCIS) diagnosed at Singapore General Hospital, for immunohistochemical expression of cytokeratin (CK) 5/6, CK14, and 34betaE12. The immunoscore (proportion of stained cells multiplied by staining intensity) was compared between the two groups. Cytokeratin expression was corroborated by confocal microscopy. Results were applied to a separate series of 43 papillary tumors from Hong Kong (HK). CK5/CK6, CK14, and 34betaE12 showed higher immunoscores in papillomas (mean values, 107.6, 186.6, and 113.1, respectively) than papillary DCIS (mean values, 12, 29.6, and 34.5, respectively; P<0.0001, P<0.001, and P<0.02, respectively). A cutoff immunoscore threshold of 50 appeared discriminatory between papilloma and papillary DCIS, and this value was applied to the HK cases, with CK5/CK6, CK14, and 34betaE12 correctly predicting 25 (89.3%), 26 (92.9%), and 27 (96.4%), respectively, of 28 HK lesions labeled as papillomas; while they corroborated 13 (86.7%), 13 (86.7%), and 5 (33.3%), respectively, of 15 HK cases diagnosed as papillary DCIS. Review of discordant cases showed that lesions were small, derived from core biopsies, or disclosed accompanying invasive carcinoma. When both SGH and HK cases were combined as a group, the sensitivity of an immunoscore of 50 or less in the diagnosis of papillary DCIS was 95%, 85%, and 62.5% for CK5/CK6, CK14, and 34betaE12, respectively, while the specificity was 86.8%, 94.3%, and 86.8%, respectively. CK immunohistochemistry can aid in evaluating papillary breast lesions. 34betaE12 does not appear as useful in identifying papillary DCIS.

Papillary carcinoma of the breast: an overview

“…Areas of usual ductal hyperplasia in a papilloma are typically characterized by strong staining of the majority of the epithelial cells in a mosaic pattern, while in contrast, malignant papillary proliferations demonstrate diminished to absent expression of high molecular weight keratins by immunohistochemical methods. [14, 21–23] It has recently been suggested that evaluation of estrogen receptor (ER) expression may be a useful adjunct to high molecular weight keratin staining, as well. In one study, a series of 82 core biopsies from papillary lesions were subjected to immunohistochemical analysis.…”

Use of immunohistochemical analysis of CK5/6, CK14, and CK34betaE12 in the differential diagnosis of solid papillary carcinoma in situ from intraductal papilloma with usual ductal hyperplasia of the breast

“…Böecker and colleagues 18 , 19 reported that a progenitor cell marker stains weakly positive around tumor cells in DCIS but stains diffusely positive in usual ductal hyperplasia. Antibodies to CK5, 7 , 18 CK5/6, 6 , 14 , 20 – 22 CK14, 6 , 20 , 22 and CK34betaE12 6 , 14 , 21 – 23 recognize these progenitor cell markers. CK5/6, CK14, and CK34betaE12 stain proliferative cells diffusely (mosaic pattern) in ductal hyperplasia and duct papillomatosis.…”

“… 14 , 24 , 25 CK14 has been reported to stain positively >95% of cells in tissue from IPUDH patients. 21 , 26 Several studies have reported that CK34betaE12 stains positively 0%–20% of tumor cells in tissue from DCIS patients. 24 , 25 , 27 However, another study reported that 40%–100% of tumor cells stain positively for CK34betaE12 in 10% of patients with DCIS.…”

Diagnosing breast lesions by fine needle aspiration cytology or core biopsy: which is better?

“…Benign papillary lesions show heterogeneous staining for ER, positive staining for myoepithelial cells and the hyperplastic epithelial cells express high molecular weight cytokeratins, whereas malignant lesions show homogeneous staining for ER, negative staining for myoepithelial cells and the hyperplastic epithelial cells are negative for high molecular weight cytokeratins. This approach had been found to be useful [58][59][60], even though false positive and false negative cases cannot be totally eliminated [56]. Thus, when dealing with a papillary lesion, both FNAC and NBC do face the same type of challenges [61], despite to a greater extent in the former, and surgical excision for full evaluation is still the optimal approach.…”