3987

LIMS1

LIM and senescent cell antigen-like domains 1;LIMS1;LIM and senescent cell antigen-like domains 1

LIM and senescent cell antigen-like-containing domain protein 1|particularly interesting new Cys-His protein 1|renal carcinoma antigen NY-REN-48

2q12.3

protein-coding

OBJECTIVE: Particularly interesting new cysteine-histidine rich protein (PINCH) is an important component of the local adhesion complexes and upregulated in several types of malignancies, and involved in the incidence and development of tumours. PINCH expression is also independently correlated with poorer survival in patients with colorectal cancer. However, there is no study of PINCH in gastric cancer, therefore, the aim of this project was to investigate PINCH expression and its clinicopathological significance in gastric adenocarcinoma. PATIENTS AND METHODS: PINCH expression was immunohistochemically examined in normal gastric mucous (n=30) and gastric adenocarcinoma (n=73), from gastric cancer patients. RESULTS: PINCH expression in the associated-stroma of gastric cancers was heterogeneous, and its positive rate (75%) was higher than that of normal gastric mucosa (43%, X^{2} =9.711, p=0.002). The stronger staining was observed at the invasive edge of tumour when compared to the inner area of tumour. The rate of positive PINCH (88%) in the cases with lymph node metastasis was higher than that (52%) in the cases without metastasis (X^{2}=11.151, p=0.001). PINCH expression was not correlated with patients gender, age, tumour size, differentiation and invasion depth (p> 0.05). COMCLUSION: PINCH protein might play an important role in the tumourigenesis and metastasis of gastric adenocarcinoma.

Particularly interesting new cysteine-histidine rich protein (PINCH), an adapter protein involved in integrin and growth factor signalling, is up-regulated in the stroma of colorectal, breast, prostate, lung and skin cancer. Strong stromal immunostaining for PINCH is an independent prognostic indicator for reduced survival in colorectal cancer, suggesting that PINCH is involved in the signalling that promotes tumour progression. Since no study on PINCH has been carried out in oral squamous cell carcinoma (OSCC), this study aimed to determine PINCH expression in OSCC and its clinicopathological significance. PINCH protein expression was examined by immunohistochemistry in 20 normal oral mucosa and in 57 OSCC specimens. The frequency of strong PINCH immunostaining was higher in tumour-associated stroma of OSCC (37%) as compared to normal oral mucosa (10%) (p=0.02). Strong PINCH stromal immunostaining predicted nodal metastasis: 19/26 (73%) OSCC cases with nodal metastasis had strong PINCH immunostaining compared to 9/31 (29%) cases without nodal metastasis (p=0.02). The PINCH expression in OSCC was more intense in stroma at the invasive edge than in intratumoural stroma. In conclusion, the up-regulation of PINCH protein in stroma may be involved in promoting invasion and metastasis in OSCC.

OBJECTIVE: Prognostic markers for pancreatic ductal adenocarcinoma (PDA) have failed to accurately predict patient prognosis. Recently, interest has developed in the accuracy of integrin-associated PINCH protein expression in human cancers as a predictive marker of tumour status. The goal of this study was to define the expression of PINCH protein in PDA. METHODS: Human PDA samples and orthotopic tumours from a murine model were analysed by immunohistochemistry for PINCH expression. In the animal model, PINCH expression was compared between primary and metastatic tumours. In the human samples, PINCH expression was correlated with stage, nodal involvement, margin status and overall survival. RESULTS: In the murine model, there was greater PINCH expression in metastatic tumours than in primary tumours. In the human PDA samples, greater staining for PINCH in the tumour cells was correlated with higher T status. Additionally, high PINCH expression in the stroma was associated with decreased overall survival. CONCLUSIONS: Findings of increased PINCH protein in more advanced stages of human PDA, as well as in metastatic tumours in the animal model, support the hypothesis that PINCH is an important controller of cell survival and migration. Additionally, the importance of the differential expression of PINCH in the human tumour and stroma warrants further evaluation.