Prognostic factors of oesophageal squamous cell carcinoma from the perspective of molecular biology

Abstract

Recent developments in molecular biology have revealed that several oncogenes, suppressor genes and adhesion molecules are involved in the development of oesophageal cancer; however, the role of these genes is still unknown. To evaluate which molecular biological factors are related to patients' prognosis and recurrence, we checked p53, p16, p21/Waf1, cyclin D1, Ki-67, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), Mdm2, Bcl2, E-cadherin and MRP1/CD9 by means of immunohistochemical analysis in 116 cases of oesophageal cancer (R0). We also checked the regrowth capability of the primary cultures of the resected tumours and the effect of post-operative treatment. Although univariate analysis revealed that pN (pTNM), pT (pTNM), sex, cyclin D1, Ki-67, VEGF, E-cadherin and cell regrowth capability were prognostic factors, multivariate analysis revealed that pN (risk ratio (RR) 3.17), sex (RR 8.13), cell regrowth capability (RR 3.03) and E-cadherin (RR 0.30) were prognostic factors. Interestingly, step-wise analysis revealed that the following five factors were prognostic factors: pN (RR 5.74), sex (RR 3.14), cyclin D1 (RR 2.29), E-cadherin (RR 0.26) and cell regrowth capability (RR 1.94). Logistic regression analysis revealed that the risk factors of haematogenous recurrence were pN (odds ratio (OR) 8.97), cyclin D1 (OR 4.52) and EGFR (OR 0.18). On the other hand, the risk factor of lymph node recurrence was pN (OR 5.16). With regard to the effect of post-operative treatment, post-operative radiotherapy was a favourable risk factor (RR 0.43) and reduced the haematogenous recurrence (OR 0.18). Our data indicate that combination analysis using pN, sex, cyclin D1, E-cadherin, EGFR and cell regrowth capability may be useful for the prediction of patient survival and recurrence. © 1999 Cancer Research Campaign

Overexpression of MDM2 protein in intrahepatic cholangiocarcinoma: relationship with p53 overexpression, Ki-67 labeling, and clinicopathological features

“…In both MDM2 and Tp53 immunostainings, cases of positive cells of 10% or more were regarded as positive, and cases of positive cells of less than 10% were categorized as negative. The cut-off points adopted to distinguish between positivity and negativity were defined as previously described [3,27,33,42,47,48]. The Ki-67 labeling index was calculated by counting positive cells among 1000 nuclei.…”

Ets-1 and VEGF expression correlates with tumor angiogenesis, lymph node metastasis, and patient survival in esophageal squamous cell carcinoma

“…Esophageal tumors show extensive local invasion and frequent spread to metastatic sites, posing a major challenge to effective management of the disease. Prediction of tumor angiogenesis by analysis of novel molecular prognostic markers might aid in developing more effective therapeutic strategies for better patient care (Shimada et al 1999;Hosch et al 2001). However, none of the molecular markers yet identified has shown unequivocal prognostic utility in EC.…”

Esophageal squamous cell carcinomas with DNA replication errors (RER + ) are associated with p16/pRb loss and wild-type p53

“…Positive criterion for immunohistochemical staining The intensity of immunohistochemical staining was evaluated in ®ve areas of the slide sections for correlation and con®rmation of the tissue analysis with speci®c criteria for each protein (Bukholm et al 1997;Gaur et al 1997;Shimada et al 1999). The results were evaluated semiquantitatively and graded on a 4-point scale on the basis of percentage of positively stained cells; ()) = immunostained positive cells not detected; (+1) = <10%; (+2) = 10± 20%; (+3) = 20±40%; (+4) = >40%.…”