4070

TACSTD2

tumor-associated calcium signal transducer 2;TACSTD2;tumor-associated calcium signal transducer 2

40kD glycoprotein, identified by monoclonal antibody GA733|cell surface glycoprotein TROP2|cell surface glycoprotein Trop-2|epithelial glycoprotein-1|gastrointestinal tumor-associated antigen GA7331|membrane component chromosome 1 surface marker 1|membran

1p32

protein-coding

PURPOSE AND EXPERIMENTAL DESIGN: To identify cancer-related genes, the expression profiles of colorectal cancer cells and normal epithelial cells were examined and compared using laser microdissection and cDNA microarray analysis. From these combined techniques, several cancer-related genes, including TROP2, were identified. TROP2 is known as a calcium signal transducer and is highly expressed in several types of tumors. However, no studies have investigated the significance of TROP2 expression in colorectal cancer. Thus, the expression status of TROP2 was investigated in 74 colorectal cancer samples by quantitative real-time reverse transcription-PCR and immunohistochemical studies. RESULTS: Laser microdissection and cDNA microarray analysis showed that there were 84 overexpressed genes in cancer cells. One of the highly overexpressed genes was TROP2. Quantitative real-time reverse transcription-PCR showed that TROP2 expression in cancer samples was significantly higher than in normal samples (P < 0.001). The samples were divided into high (n = 26) and low (n = 48) TROP2 expression groups. The cases with high TROP2 expression showed a higher frequency of liver metastasis (P = 0.005) and more cancer-related death (P = 0.046). Those cases also had an inclination of deeper depth of invasion (P = 0.064) and more lymph node metastasis (P = 0.125). Interestingly, the patients with high TROP2 expression tumors had poorer prognosis (P = 0.0036). Multivariate analysis showed that TROP2 expression status was an independent prognostic factor (relative risk, 2.38; 95% confidence interval, 1.29-4.74; P < 0.01). CONCLUSION: TROP2 is one of the cancer-related genes that correlates with biological aggressiveness and poor prognosis of colorectal cancer. Thus, TROP2 is a possible candidate gene for diagnosis and molecular target therapy of colorectal cancer.

PURPOSE: Colorectal cancer is one of the most common cancers worldwide. We tested the hypothesis that differences in the expression of certain molecular markers of colon cancer may account for different clinical outcomes. METHODS: Tissue microarray technology was used to assay the expression of 17 biological markers [beta-catenin, CD44v7, c-myc, cyclin D1, estrogen receptor beta, mitogen-activated protein kinase/extracellular signal-regulated kinase, maspin, matrix metalloproteinase-7 (MMP7), p53, Pin1, peroxisome proliferators-activated receptor-gamma, survivin, T cell transcription factor 4 (TCF4), transforming growth factor beta receptor II (TGFbetaR II), TGFbeta, TROP2, and Wnt] by immunohistochemistry in 620 colon cancer patients. The Cox proportional hazards regression model was applied to analyze the lifetime data, including time to death, time to recurrence, and time to liver metastasis. RESULTS: All the markers were present at significantly higher expression levels in tumor specimens than in normal colonic specimens. Kaplan-Meier analysis showed that high expression of TROP2, MMP7, and survivin were related to decreased survival; TCF4 and TROP2 were related to disease recurrence; and CD44v7, cyclin D1, MMP7, p53, survivin, and TCF4 were related to liver metastasis. However, the results of the multivariate analysis only showed that expression of MMP7, survivin, and TROP2 were significant predictors of lower patient survival, while TROP2 and MMP7 were significantly related to disease recurrence and liver metastasis, respectively. CONCLUSIONS: We conclude that elevated survivin, MMP7, and TROP2 expression levels are related to decreased survival. In addition, elevated MMP7 and TROP2 expression levels are predictors of disease recurrence and liver metastasis, respectively.

The GA733 gene family is composed of GA733-1 (TROP2) and GA733-2 (Ep-CAM), whose expression has been examined in various carcinomas and reported to be significantly associated with prognosis. The aim of this study was to investigate the expression of GA733 gene family members and to compare their prognostic significance in pulmonary adenocarcinoma. One hundred thirty paraffin-embedded specimens of small-sized pulmonary adenocarcinoma, less than 2 cm in diameter, were categorized using the classification of small-sized pulmonary adenocarcinoma devised by Noguchi et al. (cancer 75:2844-2852, 1995) and examined immunohistochemically using a murine monoclonal antibody against Ep-CAM and a goat polyclonal antibody against TROP2. The patient survival rate was calculated using the Kaplan-Meier method. Ep-CAM and TROP2 were similarly expressed in many small-sized pulmonary adenocarcinomas. The expression of Ep-CAM was significantly related to a favorable outcome (p = 0.0185), whereas TROP2 tended to be expressed in cases with an unfavorable outcome (p = 0.0564), and was significantly associated with an unfavorable outcome in nonlepidic-type adenocarcinomas (p = 0.0125). Multivariate analysis showed that TROP2 overexpression and lymph node metastasis were independent prognostic markers. Although the two GA733 proteins share structural similarity, they appear to have opposite biological significances in small-sized adenocarcinomas. As the expression of TROP2 was detected in more poorly differentiated tumors, the protein may have oncogenic activity.