Keratin 17 is overexpressed and predicts poor survival in estrogen receptor-negative/human epidermal growth factor receptor-2-negative breast cancer.
Clinicopathological features of breast cancer have limited accuracy to predict survival. By immunohistochemistry (IHC), keratin 17 (K17) expression has been correlated with triple-negative status (estrogen receptor [ER]/progesterone receptor/human epidermal growth factor receptor-2 [HER2] negative) and decreased survival, but K17 messenger RNA (mRNA) expression has not been evaluated in breast cancer. K17 is a potential prognostic cancer biomarker, targeting p27, and driving cell cycle progression. This study compared K17 protein and mRNA expression to ER/progesterone receptor/HER2 receptor status and event-free survival. K17 IHC was performed on 164 invasive breast cancers and K17 mRNA was evaluated in 1097 breast cancers. The mRNA status of other keratins (16/14/9) was evaluated in 113 ER-/HER2-ductal carcinomas. IHC demonstrated intense cytoplasmic and membranous K17 localization in myoepithelial cells of benign ducts and lobules and tumor cells of ductal carcinoma in situ. In ductal carcinomas, K17 protein was detected in most triple-negative tumors (28/34, 82%), some non-triple-negative tumors (52/112, 46%), but never in lobular carcinomas (0/15). In ductal carcinomas, high K17 mRNA was associated with reduced 5-year event-free survival in advanced tumor stage (n = 149, hazard ratio [HR] = 3.68, P = .018), and large (n = 73, HR = 3.95, P = .047), triple-negative (n = 103, HR = 2.73, P = .073), and ER-/HER2-(n = 113, HR = 2.99, P = .049) tumors. There were significant correlations among keratins 17, 16, 14, and 9 mRNA levels suggesting these keratins (all encoded on chromosome 17) could be coordinately expressed in breast cancer. Thus, K17 is expressed in a subset of triple-negative breast cancers, and is a marker of poor prognosis in patients with advanced stage and ER-/HER2-breast cancer.
Department of Pathology, Stony Brook University School of Medicine, New York, NY 11794-8691, USA. Electronic address: ross.merkin@gmail.com.
Ross D
RD
Merkin
Department of Pathology, Stony Brook University School of Medicine, New York, NY 11794-8691, USA; Department of Biomedical Informatics, Stony Brook University School of Medicine, New York, NY 11794-8691, USA. Electronic address: elizabeth.vanner@stonybrook.edu.
Elizabeth A
EA
Vanner
Department of Surgery, Stony Brook University School of Medicine, New York, NY 11794-8691, USA. Electronic address: Jamie.Romeiser@stonybrookmedicine.edu.
Jamie L
JL
Romeiser
Department of Surgery, Stony Brook University School of Medicine, New York, NY 11794-8691, USA. Electronic address: AnnieLaurie.Shroyer@stonybrookmedicine.edu.
A Laurie W
ALW
Shroyer
Department of Pathology, Stony Brook University School of Medicine, New York, NY 11794-8691, USA. Electronic address: Luisa.EscobarHoyos@stonybrook.edu.
Luisa F
LF
Escobar-Hoyos
Department of Pathology, Stony Brook University School of Medicine, New York, NY 11794-8691, USA. Electronic address: Jinyu.Li.1@stonybrook.edu.
Jinyu
J
Li
Department of Pathology, Stony Brook University School of Medicine, New York, NY 11794-8691, USA. Electronic address: Robert.Powers@stonybrookmedicine.edu.
Robert S
RS
Powers
Department of Pathology, Stony Brook University School of Medicine, New York, NY 11794-8691, USA. Electronic address: Stephanie.Burke@stonybrookmedicine.edu.
Stephanie
S
Burke
Department of Pathology, Stony Brook University School of Medicine, New York, NY 11794-8691, USA. Electronic address: Kenneth.Shroyer@stonybrookmedicine.edu.
Kenneth R
KR
Shroyer
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D057225:Data Mining; D030541:Databases, Genetic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053537:Keratin-17 / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D012042:Registries; D012307:Risk Factors; D013997:Time Factors; D064726:Triple Negative Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D053537:Keratin-17; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human
Breast cancer; Immunohistochemistry; Keratin