Abstract
BackgroundThe adaptor protein PINCH is overexpressed in the stroma of several types of cancer, and is an independent prognostic marker in colorectal cancer. In this study we further investigate the relationship of PINCH and survival regarding the response to chemotherapy in colorectal cancer.ResultsParaffin-embedded tissue sections from 251 primary adenocarcinomas, 149 samples of adjacent normal mucosa, 57 samples of distant normal mucosa and 75 lymph node metastases were used for immunohistochemical staining. Stromal staining for PINCH increased from normal mucosa to primary tumour to metastasis. Strong staining in adjacent normal mucosa was related to worse survival independently of sex, age, tumour location, differentiation and stage (p = 0.044, HR, 1.60, 95% CI, 1.01-2.52). PINCH staining at the invasive margin tended to be related to survival (p = 0.051). In poorly differentiated tumours PINCH staining at the invasive margin was related to survival independently of sex, age and stage (p = 0.013, HR, 1.90, 95% CI, 1.14-3.16), while in better differentiated tumours it was not. In patients with weak staining, adjuvant chemotherapy was related to survival (p = 0.010, 0.013 and 0.013 in entire tumour area, invasive margin and inner tumour area, respectively), but not in patients with strong staining. However, in the multivariate analysis no such relationship was seen.ConclusionsPINCH staining in normal adjacent mucosa was related to survival. Further, PINCH staining at the tumour invasive margin was related to survival in poorly differentiated tumours but not in better differentiated tumours, indicating that the impact of PINCH on prognosis was dependent on differentiation status.
Highlights
The adaptor protein PINCH is overexpressed in the stroma of several types of cancer, and is an independent prognostic marker in colorectal cancer
In the univariate analysis we found chemotherapy to be significantly related to survival in patients with weak stromal staining for PINCH at the invasive margin, while in patients with strong staining there was no relationship between chemotherapy and survival
Stromal immunohistochemical staining for PINCH in normal mucosa adjacent to a tumour was found to be related to survival in colorectal cancer patients
Summary
The adaptor protein PINCH is overexpressed in the stroma of several types of cancer, and is an independent prognostic marker in colorectal cancer. PINCH, interesting new cystein-histidinerich protein, was first identified in 1994 as an evolutionary conserved protein belonging to the LIM family, consisting of five LIM domains [1]. The PINCH gene is located to chromosome 2q12.2 and encodes a protein that functions as an adaptor protein [3]. PINCH is known to directly associate with two proteins: integrin-linked kinase (ILK) [4] and Nck-2 [5]. ILK is an intracellular serine/threonine protein kinase that is a constituent of integrin-mediated cell-matrix focal adhesions, structures that mediate cell adhesion and signal transduction between the extracellular matrix and the intracellular compartment [6].
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