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.

Background and Purpose: An exon 2 G4C14A4T14 polymorphism in the p73 gene was

Lööf et al 3 ABSTRACTp73 can activate transcription of p53-responsive genes, thereby inhibiting cell growth. An alternative promoter in the TP73 gene gives rise to an N-terminally truncated isoform of p73, ∆Np73, which lacks the transactivation domain of the full length TAp73 protein. TAp73 is considered pro-apoptotic, and ∆Np73 antiapoptotic. In this study, we overexpressed ∆Np73β in p53 wild type and p53 mutant colon cancer cell lines and further exposed the cells to cancer therapeutic drug cisplatin. The results showed that cisplatin decreased the protein expression levels of ∆Np73β in a dose-dependent manner, and both TAp73 and p53 were upregulated after cisplatin treatment. Further, clonogenic potential and cell viability were decreased, and apoptotic cells increased, in p53 mutant and in p53 wild type cells.Cellular viability was significantly higher in ∆Np73β-cells than mock-transfected cells. However, ∆Np73β overexpression did not affect the cellular susceptibility to cisplatin. In conclusion, the overexpression of ∆Np73β increases viability in p53 wild type and p53 mutant colon cancer cells, and cisplatin induces the degradation of ∆Np73β in a dose-dependent manner.