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Background Various biomarkers are being developed for the early diagnosis of cancer and for predicting its prognosis. The aim of this study is to evaluate the diagnostic significance of serum CD109 in head and neck squamous cell carcinoma (HNSCC). Methods The serum CD109 levels in a total of 112 serum samples collected before and after surgery from 56 HNSCC patients were analyzed with an enzyme‐linked immunosorbent assay (ELISA). The clinical factor that showed a statistically significant association with both the preoperative serum CD109 level, and the CD109 index: which was defined as the ratio of the preoperative serum CD109 level to the postoperative serum CD109 level, were assessed. The correlations between the serum CD109 levels and lymph node density (LND), pathological features such as lymphatic invasion, and serum SCC antigen levels were also assessed. Results The ELISA measurement revealed that preoperative serum CD109 levels were elevated in patients with node metastasis‐positive and stage IV disease, in comparison to those with node metastasis‐negative and Stage I+II+III disease, respectively. A multiple regression analysis indicated that serum CD109 level was significantly associated with the node metastasis status. A Spearman's rank correlation analysis also revealed a positive correlation between the preoperative serum CD109 level and LND. Furthermore, the probabilities of the overall and relapse‐free survival were significantly lower in patients with a preoperative serum CD109 level of ≥38.0 ng/ml and a CD109 index of ≥1.6, respectively, than in others. There was no significant correlation between the serum CD109 and SCC antigen levels. Conclusions The serum CD109 levels were elevated in patients with advanced stage disease, reflecting the node metastasis status. CD109 in sera could be a novel prognostic marker for HNSCC involving lymph node metastasis., The serum CD109 levels in a total of 112 serum samples collected before and after surgery from 56 head and neck squamous cell carcinoma patients were analyzed with an enzyme‐linked immunosorbent assay. The serum CD109 levels were elevated in patients with advanced stage disease due to the node metastasis status, and the probability of overall and relapse‐free survival was significantly lower in patients with a high levels of serum CD109. CD109 in sera could be a novel prognostic marker for head and neck squamous cell carcinoma involving lymph node metastasis.

Bladder cancer is one of the most common malignant diseases. Since a high-rate of recurrence is a serious problem for early stage urothelial carcinomas, new strategies for the management of recurrent urothelial carcinomas have been explored. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein and is expressed in various cancer tissues, mainly squamous cell carcinomas. CD109 negatively controls transforming growth factor (TGF)-β/Smad signaling in vitro. In this study, we analyzed the clinical significance of CD109 expression in bladder cancer using immunohistochemistry. Of 156 urothelial carcinoma tissues, 69.9% were positive for CD109, whereas CD109 was not expressed in seven normal bladder epithelia. CD109 expression was significantly higher in non-muscle-invasive (pTa+pT1) or low-grade (G1+G2) tumors than in muscle-invasive (pT2-4) or high-grade (G3) tumors, and was associated with cancer-specific survival. Simultaneous immunostaining of CD109 and phosphorylated Smad2 showed an inverse immunoreactivity relationship between the two, suggesting that CD109 inhibits TGF-β/Smad signaling in tumor tissues. Interestingly, CD109 was found to be highly expressed in the basal layer of non-invasive urothelial carcinomas, and the expression pattern was similar to that of CD44, a marker of cancer stem cells. These findings suggest that CD109 is involved in bladder tumorigenesis and is a potential target for cancer immunotherapy.

Breast cancer can be classified into several subtypes based on gene expression profiling. Basal-like breast carcinoma (BLC) has a triple negative phenotype, that is, the subtype lacks the estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2). It has been recently reported that CD109, a glycosylphosphatidylinositol (GPI)-anchored cell surface protein, is a new breast myoepithelial marker. In the present study CD109 expression was investigated in invasive ductal carcinomas (IDC) of the breast on immunohistochemistry. Eighty-eight formalin-fixed, paraffin-embedded breast carcinoma sections were immunostained with anti-CD109, anti-cytokeratin 5/6 (CK5/6), anti-calponin, anti-vimentin and anti-p63 antibodies. CD109 expression was detected in 18 of 30 basal-like breast carcinomas (BLC) but not in other types of 53 IDC (non-BLC) that were positive for ER, PgR and/or HER2. The percentage of CD109-positive tissues (60%) in BLC was similar to that of CK5/6 (63%) and higher than that of other myoepithelial markers including p63 (23%), calponin (33%) and vimentin (33%). Statistical analysis indicated that the CD109-positive group in BLC, but not the CK5/6-positive group in BLC, was associated with reduced fat invasion (P < 0.05). These findings indicate that CD109 is a useful diagnostic marker for BLC and that CD109 expression may affect biological properties of cancer cells.

The CD109 gene encodes a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. Herein it is shown that CD109 is highly expressed in myoepithelial cells of mammary, salivary, and lacrimal glands; and in prostate basal cells. The anti-CD109 antibody generated by the authors was available for formalin-fixed paraffin section, and it strongly stained myoepithelial cells and basal cells but not ductal, acinar, and secretory cells in these glands. CD109 expression was negative in examined breast ductal carcinomas and prostate adenocarcinomas. These findings indicate that CD109 is a useful marker for the diagnosis of invasive breast and prostate carcinomas.

CD109 is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein whose expression is up-regulated in squamous cell carcinomas (SCCs) of the lung, esophagus, and uterus. The purpose of this study was to evaluate CD109 expression in oral tumors, including premalignant lesions, and to assess the clinical application of CD109 in oral cancer. CD109 expression in oral normal and tumor tissues from 124 patients was examined by immunohistochemical staining with anti-CD109 antibody, and significant relations between clinical features and CD109 expression were statistically assessed. We found that high levels of CD109 expression were frequently detected in SCCs and premalignant lesions of the oral cavity, but not in normal squamous epithelia. The CD109 expression level was higher in well-differentiated SCCs than in poorly differentiated SCCs. Furthermore, premalignant lesions highly expressing CD109 showed higher risk to progress to SCCs. Oral SCC cell lines overexpressing CD109 exhibited accelerated cell growth in vitro compared with control cell lines. In addition, overexpression of CD109 impaired the transforming growth factor (TGF)-beta1-mediated suppression of cell growth. These findings suggest that CD109 plays a role in the development of oral cancers, and is a useful prognostic marker to predict malignant transformation of premalignant lesions.