Tetraspanin CD151 is a novel prognostic marker in poor outcome endometrial cancer

Abstract

Background:Type II cancers account for 10% of endometrial cancers but 50% of recurrence. Response rates to chemotherapy at recurrence are poor and better prognostic markers are needed to guide therapy. CD151 is a small transmembrane protein that regulates cell migration and facilitates cancer metastasis. High CD151 expression confers poor prognosis in breast, pancreatic and colorectal cancer. The prognostic significance of tetraspanin CD151 expression in poor outcome endometrial cancers was evaluated, along with oestrogen receptor (ER), progesterone receptor (PR), p53, human epidermal growth factor receptor -2 (HER-2), and CD 151 staining compared with α6β1, α3β1 integrins, and E-cadherin.Methods:Tissue microarray constructed from 156 poor outcome endometrial cancers, tested with immunohistochemistry and staining correlated with clinicopathological data were used. A total of 131 data sets were complete for analysis.Results:Expression of CD151 was significantly higher in uterine papillary serous and clear cell carcinoma than in grade 3 endometrioid carcinoma, sarcoma or carcinosarcoma (P<0.001). In univariate analysis, age, stage, histology type and CD151 were significant for both recurrence free (RFS) and disease specific survival (DSS). In multivariate analyses, CD151 was significant for RFS and DSS (P=0.036 and 0.033, respectively) in triple negative (ER, PR and HER-2 negative) tumours (88/131). The HER-2, p53, ER and PR were not prognostic for survival. There was strong concordance of CD151 with E-cadherin (98%), but not with α6β1 (35%), α3β1 staining (60%).Conclusion:The CD151 is a novel marker in type 2 cancers that can guide therapeutic decisions. CD151 may have an important role in tumourigenesis in some histology types.

CD151 represses mammary gland development by maintaining the niches of progenitor cells

“…Furthermore, the notion of CD151 as a tumor suppressor is supported by multiple clinical analyses of this molecule in several other types of human cancer, including bladder, endometrial and possibly colon cancer. [55][56][57] Hence, as a multi-faceted molecule, the functional role of CD151 during cancer development is likely linked to the cellular origin or oncogenic context of tumor-initiating cells as implicated for many adhesion molecules including integrins and their downstream effectors. [58][59][60][61] In summary, our current study demonstrates that tetraspanin CD151 contributes to the pubertal development of mammary glands by maintaining the normal activity of adult epithelial progenitor cells and ECM homeostasis.…”

Genetic Ablation of the Tetraspanin CD151 Reduces Spontaneous Metastatic Spread of Prostate Cancer in the TRAMP Model

“…7,8) has been shown in clinical studies to have a positive correlation with poorer patient outcomes in a variety of cancers including prostate (9), lung (10), colon (11), breast (12,13), renal (14) and endometrial cancers (15). Molecular studies involving CD151 with cancer progression and metastasis to date have focused on in vitro and grafting models.…”

Triple negative endometrial cancer

“…The existing studies have reported significantly higher CD151 expression in triple negative endometrial cancer as compared to other histological types. Increased CD151 expression is the basis for worse prognosis [15]. Likewise, higher CD151 expression in triple negative breast cancer is associated with shorter survival time and poorer prognosis [32].…”

“…However, to the best of our knowledge, only 4 papers have dealt with triple negative EC [13][14][15][16].…”