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BACKGROUND: Bevacizumab, an angiogenesis inhibitor is used in regimens for metastatic colorectal cancer (CRC). A minority of cancer cells with characteristics of cancer stem cells (CSC) may be responsible for progression and development of chemotherapy resistance in this disease. CD133 is a well-known CSC marker and is associated with angiogenesis, poor prognosis and resistance to chemotherapy. OBJECTIVE: The purpose of our study was to evaluate the association between the rs3130 and rs2286455 polymorphisms of the CD133 gene and the response, toxicity, and overall survival of patients with CRC on bevacizumab-based treatment. METHODS: Forty-three patients receiving bevacizumab, irinotecan and capecitabine and 15 patients receiving bevacizumab, irinotecan and 5-FU were included. Efficacy and toxicity were evaluated. KRAS mutation analysis and rs3130 and rs2286455 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR-RFLP. RESULTS: No association between KRAS mutated alleles and response was found. The rs3130 CC genotype was associated with reduced toxicity of treatments (p = 0.0017), and with lower overall survival on bevacizumab (p = 0.002). CONCLUSIONS: The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the inflammatory mass in abdominal wall imitating a drain site recurrence following rectal cancer surgery.

Purpose: Laparoscopic colectomy has been reported as a safe and oncologically similar operation to open colectomy. A number of expensive surgical instruments are necessary for the procedure which should be applied if it is cost-effective for the patient and the health system in general. The purpose of the current study was the economic evaluation of laparoscopic compared to open colectomy for the treatment of colon cancer in the Greek national health system., Methods: Fifty patients undergoing open colectomy and 42 undergoing laparoscopic colectomy were enrolled in this case-control study. Length of hospital stay, duration of operation, complication rates, cost of equipment used, total costs and three questionnaires measuring quality of life /QoL (EQ-5D, SF-36 and QLQ-C30) at baseline, 1 and 3 months after the operation were recorded., Results: No statistically significant difference in QoL measured by QALYs between laparoscopic and open colectomy was observed. On the other hand, cost utility analysis revealed that laparoscopic colectomy was more expensive considering the advantages it offers., Conclusions: Laparoscopic colectomy is not superior to open colectomy on a QoL basis in the Greek public hospital system and is less cost-effective compared to the open procedure. Since the expensive equipment used in laparoscopic colectomy seems to be the causative factor for the high cost of this type of operation, an effort should be made to reduce it either by using reusable instruments or by implementing policies aiming at suppliers cutting down equipment charges.

Loss of basement membrane integrity during neoplastic invasion may have some direct prognostic significance, which is worth investigating. We studied 151 cases of colorectal adenocarcinomas retrospectively. The aim of the study was to investigate the immunohistochemical expression as well as the distribution of laminin and collagen IV within the basement membranes of cancer cell formations. The results were related to histological grade of malignancy (I, II or III) and Dukes' staging of all tumours as well as to 3-year survival status in 52 patients. Using the immunostaining method of strept ABComplex/HRP and appropriate monoclonal or polyclonal antibodies, we assessed the continuity, the discontinuity of the distribution or the total loss of structural basement membrane components alongside the infiltrating borders of each tumour. The results were evaluated statistically. Either a considerable degree of discontinuity or a total loss of basement membrane components was more common in moderately and poorly differentiated adenocarcinomas (p = 0.002 and p = 0.005 for collagen IV and laminin, respectively) and they seemed to be adversely associated with survival status (p = 0.066 and p = 0.014 for collagen IV and laminin, respectively). Interestingly, no association with the stage of disease was noticed. The results of this study reinforce the value of laminin and collagen IV as possible prognostic factors independently to tumour stage. The total loss or considerable discontinuity of the basement membranes of cancerous cells can be considered as indicators of tumour aggressiveness.

The case of a 37-year-old Caucasian female with a history of systemic lupus erythematosus, admitted to hospital due to progressively worsening abdominal pain and arthralgia. During hospitalisation, signs of acute abdomen developed. Laparotomy revealed perforation of the rectum, accompanied by necrosis of the rectosigmoid. Histologic examination revealed vasculitis involving small- and medium-sized vessels. This case report emphasizes the point that colonic and especially rectal involvement from vasculitis, though unusual, may present with profound and possibly life-threatening manifestations and stresses the difficulties in clinical and histological differential diagnosis from other causes of systemic lupus erythematosus-associated abdominal pain.

Background and Objectives: Cathepsin D (CD), an estrogen-regulated lysosomal protease, has been detected in a variety of tissues. CD expression has been correlated with the invasive potential of breast cancer, acting as an autocrine mitogen or as a protease that degrades the extracellular matrix. The role of CD expression in predicting prognosis or invasive potential in colorectal carcinomas is mostly unknown., Methods: CD immunohistochemical expression was studied in 60 surgical specimens of colon adenocarcinomas. A three-step avidin biotinylated, horseradish immuno-peroxidase (ABC-HRP) staining technique was performed on 4 microm paraffin-embedded tissue sections with a polyclonal antibody to CD., Results: Carcinoma cells showed positive CD immunostaining in 41.6% of adenocarcinomas (50%, 43.7%, 37.5%, and 25% of Dukes' Stage A, B, C, and D, respectively). Nonneoplastic stromal cells demonstrated positive staining in 68.3% of the adenocarcinoma specimens (37.5%, 62.5%, 91.6%, and 75% of Stage A, B, C, and D, respectively). Patients with colorectal carcinomas exhibiting simultaneously negative and positive CD expression in malignant and stromal cells, respectively, had a worse 5-year overall survival (P < 0.05). The mean 5-year survival of the 16 patients overexpressing CD in nonneoplastic stromal cells (>15% of stromal cells positive for CD) was significantly worse in comparison with the rest of the adenocarcinomas (n = 44) (27.6 +/- 4.6 vs. 46 +/- 2.7 months, respectively, P < 0.01)., Conclusions: Expression of CD immunoreactivity by the stromal cells may be associated with a more invasive phenotype. Therefore, CD expression in tumor and stromal cells may serve as an important indicator of progression and guide postoperative treatment.

Background: Cathepsin D (CatD) can facilitate the invasive behaviour of breast cancer cells and thus plays a key role in the mechanism of invasion and metastasis., Materials and Method: The expression of the protease CatD was evaluated using an immunohistochemical technique with a polyclonal antibody on paraffin-embedded tissue from 80 women treated for invasive ductal mammary carcinoma not otherwise specified (NOS)., Results: Thirty seven tumours (46%) showed prominent staining of cells in the tumour. Neoplastic cell staining for CatD correlated with axillary nodal involvement (p < 0.05), high oestrogen receptor positivity status (p < 0.01) and low or moderate tumour grade (p < 0.05). Stromal cell (primarily histiocyte) CatD immunostaining was frequently noticed and was proportional to the degree of the intratumoural inflammatory infiltrate., Conclusions: Cat D detection in neoplastic cells is likely to be involved in the invasive capability of well differentiated breast cancer cells, but it may simultaneously reflect the functional integrity of the oestrogen response pathway, commonly observed in well-differentiated tumours.

The immunohistochemical expression of p53 and c-erbB-2 gene proteins was examined in a series of 130 breast adenocarcinomas. This study intended to investigate whether the frequency of the altered expression of the tumour suppressor gene p53 and the overexpression of the oncogene c-erbB-2 in breast cancer tissue cells correlated with other variables known to affect the biological behaviour of these tumours and the overall survival of the patients (median follow-up time: 6 years). The expression of p53 protein and c-erbB-2 gene product was evaluated immunohistochemically. Expression of p53 protein was detected in 30 (23 per cent) of the neoplasms examined, while 26 (20 per cent) out of the 130 cases demonstrated positive c-erbB-2 immunoreactivity. There was a statistically significant association between p53 protein expression and primary tumour size, lymph node involvement, and oestrogen receptor positivity. The incidence of c-erbB-2 positivity was significantly correlated with high tumour grade, axillary node invasion, large tumour size, and the absence of steroid receptors. p53 immuno-expression was clearly associated with c-erbB-2 protein overexpression. Concomitant p53 and c-erbB-2 positive immunolabelling, which emerged in 14 out of the 130 cases (10.7 per cent), was clearly associated with high grade, large size, positive nodal status, ductal infiltrating (NOS) histological type, and low values of progesterone receptors. Overall survival of patients was not significantly related to the immunoreactivity of either p53 or c-erbB-2 considered separately, whereas there was a clearly significant trend to worse overall prognosis in cancers with double p53/c-erbB-2 positive phenotype. The simultaneous immunodetection of p53/c-erbB-2 appears to have greater negative prognostic relevance than their separate expression.

Purpose: The expression of 70,000-Da heat shock protein (HSP 70) and HLA-DR molecules on cancer cells influences immunologic mechanisms that may be of some prognostic significance. The purpose of this study was to examine the relationship among immunohistochemical HSP 70, HLA-DR expression, and clinicopathologic tumor variables, as well as patient survival in a series of 128 colorectal carcinomas., Method: A three-step immunoperoxidase staining technique was undertaken for detection of both markers., Results: Of the examined carcinomas 77.3 percent were HSP 70-positive and 74.2 percent were HLA-DR-positive. Increased HSP 70-positive expression correlated significantly with low differentiation (P < 0.05), showed a tendency to characterize advanced stages of disease, and was clearly associated with worse overall survival (P < 0.05). The highest rate of HLA-DR positivity was demonstrated in early stages and was significantly associated with more favorable prognosis (P < 0.001). HSP 70-positive/HLA-DR-negative patients had worse overall survival compared with the rest (P < 0.001)., Conclusions: The resulting opposite effects on prognosis of examined markers seem to be related to different pathophysiologic functional roles on tumor immunology.

Mutant p53 tumour suppressor gene and c-erbB-2 proto-oncogene are involved in human carcinogenesis, and their protein product detection in human malignancies might influence the evolution of many neoplasms. Our aim was to estimate their association with histopathological and clinical parameters of prognostic value in colorectal cancer. An immunohistochemical assay was undertaken in formalin-fixed sections from tissue specimens of 60 colorectal carcinomas. Nuclear p53 expression was detected in 46.6%, while membranic c-erbB-2 positivity was noticed in 35% of the examined cases. P53 positivity rate significantly correlated with poor differentiation (p < 0.001), high mitotic activity (p < 0.0001), tumour stage (p < 0.001) and 5-year overall survival period (p < 0.01). C-erbB-2 positivity incidence significantly correlated with advanced Dukes' stage (p < 0.001) and high mitotic activity (p < 0.05). Significant association between p53 and c-erbB-2 immunostaining was observed (p < 0.05) and p53/c-erbB-2 co-expression was related to poor differentiation (p < 0.001), high mitotic activity (p < 0.001), advanced Dukes' stage (p < 0.001), tumour aneuploidy (p < 0.05) and worse overall survival (p < 0.05). P53 and c-erbB-2 immunohistochemical detection in combination with known prognostic indicators may be a useful future tool in determining colorectal cancer prognosis and subsequently in deciding on optimal postoperative treatments.

Estrogen receptors (ERs) have recently been reported to be present in carcinomas of stomach, an organ that has so far been considered as nontarget for sex hormones. Cathepsin D is an estrogen-regulated lysosomal protease that has been overexpressed in breast cancer. ER and cathepsin D immunohistochemical expression were studied in this research in order to estimate their association to known histopathological and clinical parameters and their possible prognostic significance as well. Sixty-two patients with gastric adenocarcinomas were included in this study. The cancers were studied immunohistochemically concerning ER positivity in tumor cell nuclei and cathepsin D cytoplasmic expression. Nuclear ER staining was detected in tumor cells of 25% of male and 27% of female patients. ER positivity was demonstrated mainly in the well and moderately differentiated carcinomas; 87.5% of ER(+) tumors were also characterized as cathepsin D positive and a significant correlation between ER and cathepsin D positive expression was demonstrated (P < 0.05). Cytoplasmic cathepsin D expression was observed in carcinomatous cells of 70.9% of gastric tumors. Early tumor stage and good differentiation were significantly associated with increased cathepsin D expression (P < 0.05, P < 0.001). Histologic type, degree of differentiation and tumor stage were significantly correlated to survival (P < 0.05, P < 0.001 and P < 0.001). The patients who were cathepsin D(+) had a significant prognostic advantage over the cathepsin D(-) patients (P < 0.001). The presence of ER and estrogen-regulated cathepsin D indicates the involvement of sex hormonal factors in these tumors and cathepsin D positive expression in tumor cells seems to be related to better prognosis. Their biological, clinical, and prognostic roles remain to be further elucidated.

Purpose: Proliferating cell nuclear antigen immunohistochemical expression and flow cytometry techniques were used in this study to estimate the proliferation tendency and biologic aggressiveness in benign and malignant epithelial tumors of the colon and rectum., Methods: Thirty-five adenomas and 60 adenocarcinomas were studied immunohistochemically concerning proliferating cell nuclear antigen positivity in tumor cell nuclei. In addition, flow cytometry techniques were used to estimate the DNA content and percentage of tumor cells in the S-phase., Results: The mean proliferating cell nuclear antigen score for adenomas was 38 percent compared with a mean score of 50.4 percent for adenocarcinomas that were studied (P < 0.05). In dysplastic areas of malignantly transformed adenomas (n = 5), the highest proliferating cell nuclear antigen score (80 percent) was focally observed. Taking flow cytometry parameters into account, we found out that proliferating cell nuclear antigen can be used as an indirect indicator of the number of cells in the S-phase (SPF) but not as an independent prognostic factor. Statistical significance was found between Type III (aneuploid carcinomas) and increased proliferating cell nuclear antigen expression (proliferating cell nuclear antigen score > or = 60 percent). Furthermore, aneuploidy was especially found on cancer located on the left colon (44 percent vs. 14 percent of right colon neoplasms). Considering DNA ploidy of the above neoplasms, the aneuploid adenocarcinomas had a tendency for poorer prognosis especially if they were related to Dukes Stage C female patients., Conclusions: The comparative assessment of the above parameters might be of considerable importance in the study of the proliferation activity of any form of colorectal neoplasia.