title: Clinicopathologic features of molecular subtypes of triple negative breast cancer based on immunohistochemical markers.
abstract: This study was performed to identify molecular subtypes of triple negative breast carcinoma (TNBC) based on immunohistochemical markers. We prepared a tissue microarray from TNBC specimens of 122 patients and performed immunohistochemical staining for cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR), claudin 3, claudin 4, claudin 7, E-cadherin, androgen receptor (AR), and gammma-glutamyltransferase (GGT1). Based on immunoreactivity, tumors were classified into basal-like (CK5/6 positive and/or EGFR positive), molecular apocrine (AR positive and/or GGT1 positive), claudin low (claudin 3, claudin 4, claudin 7 negative and/or E-cadherin negative), mixed (tumors belonging to two or more subtypes), and null (tumors not matching any other subtypes). The TNBC specimens of 122 patients included 27 basal-like (22.1%), 28 claudin low (23.0%), 12 molecular apocrine (9.8%), 23 mixed (18.9%) and 32 null (26.2%) subtype tumors. The molecular apocrine subtype showed the highest percentage of apocrine differentiation and the lowest Ki-67 labeling index (p<0.001 and p=0.040, respectively). In univariate analysis, tumor cell discohesiveness was related with shorter disease free survival (DFS) and overall survival (OS) (p=0.005, and 0.002, respectively). In multivariate analysis, tumor cell discohesiveness was related with shorter OS and CK5/6 positivity (p=0.018), and claudin 7 positivity (p=0.019) was related with shorter DFS. In conclusion, using immunohistochemical staining for CK5/6, EGFR, claudin 3, claudin 4, claudin 7, E-cadherin, AR, and GGT1, we categorized TNBC into a basal-like subtype, a claudin low subtype, a molecular apocrine subtype, a mixed subtype showing characteristics of two different subtypes, and a null subtype not belonging to any of the subtypes identified.
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju,  South Korea.
authors.forename: Junjeong
authors.initials: J
authors.lastname: Choi
authors.forename: Woo-Hee
authors.initials: WH
authors.lastname: Jung
authors.forename: Ja Seung
authors.initials: JS
authors.lastname: Koo
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D057167:Claudins / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053555:Keratin-5 / Q000378:metabolism; D053553:Keratin-6 / Q000378:metabolism; D008875:Middle Aged; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D057167:Claudins; D053555:Keratin-5; D053553:Keratin-6; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D005723:gamma-Glutamyltransferase; C512478:EGFR protein, human; D066246:ErbB Receptors