Expression and potential role of ErbB receptors in type II endometrial cancer.

OBJECTIVE: Endometrial cancer is the most common malignancy of the female genital tract. Based on clinical and pathological features, endometrial cancer is classified into two types. The aim of our study was to describe the expression and the potential clinical role of ErbB receptors in Greek patients with type II endometrial cancer. STUDY DESIGN: Between 1991 and 2008, 10 women with histologically confirmed type II endometrial cancer were referred to the Department of Gynecologic Oncology of the University of Patras Medical School. Tissue specimens from endometrial lesions were immunostained for EGFR, ErbB-2, ErbB-3 and ErbB-4. RESULTS: For EGFR, 5 cases were positive (50%) and 5 cases were negative. For ErbB-2, 9 cases were positive (90%) and 1 case was negative. For ErbB-3, all cases were positive. For ErbB-4, 7 cases were positive (70%) and 3 cases were negative. Also for all ErbB receptors, 5 cases were positive (50%). During follow up, 3 patients died from their disease. All of them had papillary serous endometrial cancer and 2 of them were positive for all ErbB receptors. CONCLUSION: Although our study was based on a small number of cases, it is obvious that we had high expression levels of ErbB receptors in patients with type II endometrial cancer. Also the majority of patients with dismal outcome were positive for all ErbB receptors. This is very important, as ErbB-targeted therapies may be clinically active as adjuvant therapy in well-defined subgroups of type II EC patients with EGFR and ErbB-2 overexpression.

Complications and risk factors related to the extent of surgery in thyroidectomy. Results from 2,043 procedures.

OBJECTIVE: To evaluate the rate of complications and the risk factors in relation to the extent of surgery in patients undergoing thyroidectomy in a tertiary university center. DESIGN: Data were collected retrospectively from 2,043 consecutive patients who underwent thyroid surgery for various thyroid diseases at the University Hospital of Patras, Greece, between January 1996 and December 2007. Recurrent laryngeal nerve palsy (RLNP) and hypoparathyroidism were set as the primary end points, while hematoma and wound infection were set as the secondary endpoints. RESULTS: Total, near-total and subtotal thyroidectomy was performed in 1,149,777 and 117 patients, respectively. Transient RLNP occurred in 34 (1.6%) and permanent in 19 (0.9%) patients. Multivariate logistic regression analysis showed that extended resection (OR-odds ratio-1.6), Graves' disease (OR 2.7), thyroiditis (OR 2.1), recurrent goiter (OR 2.3) and thyroid malignancy (OR 1.7) were all independent risk factors for transient RLNP, whereas Graves' disease (OR 2.2) and recurrent goiter (OR 1.7) emerged as independent risk factors for permanent RLNP. The rates of transient and permanent hypoparathyroidism were 27.8% and 4.8%, respectively. Multivariate analysis for transient hypoparathyroidism revealed that the extent of surgical resection (OR 2.2), Graves' disease (OR 2.1), recurrent goiter (OR 1.7), female gender (OR 1.5) and specimen weight (OR 1.6) were independent predictors. However, the extent of surgical resection (OR 2.7), Graves' disease (OR 1.8), recurrent goiter (OR 1.5) and malignant disease (OR 1.5) were independent risk factors for permanent hypoparathyroidism. Postoperative wound infection and hematoma occurred in 6 (0.3%) and 27 (1.3%) patients, respectively. No correlation was observed between wound infection or postoperative hemorrhage and the extent of surgery. CONCLUSIONS: Despite the higher morbidity, total thyroidectomy is emerging as an attractive surgical option even for benign thyroid disease due to the risk of subclinical (occult) malignancy, the possibility of goiter relapse as well as of the increased risk of complications following reoperation.

The potential role of Bcl-2 expression, apoptosis and cell proliferation (Ki-67 expression) in cases of gastric carcinoma and correlation with classic prognostic factors and patient outcome.

BACKGROUND: This study investigated the presence of apoptosis and proliferation in gastric cancer and assesses their possible correlation with classic prognostic markers and patients' survival. PATIENTS AND METHODS: The study comprised 110 patients with gastric carcinoma who underwent gastrectomy for therapeutic reasons, and did not receive any pre- or postoperative treatment. Patients were followed up for 3.5-140 months. Thick paraffin sections (4 microm) were subjected to immunohistochemistry using anti-Bcl-2 and anti-Ki-67 antibodies and to in situ hybridization [TUNEL method-apoptotic body index (ABI)]. Morphological and immunohistochemical results were correlated with clinicopathologic parameters. RESULTS: Bcl-2 protein was detected in 67% of adenocarcinomas with increased expression in low-grade and early-stage tumors. Bcl-2 expression did not correlate with Ki-67 index, ABI or patients' survival. Ki-67 expression was correlated with a poorer survival rate. Apoptosis was more frequently observed in advanced stage and high-grade tumors. Cox analysis revealed that tumor stage and grade, as well as Ki-67 index, constituted independent prognostic factors. CONCLUSION: This study included patients with gastric cancer none of whom received any additional pre- or post-operative treatment. Thus the prognostic value of each marker studied was not affected by additional treatments. Bcl-2 expression in advanced-stage and high-grade gastric carcinomas, indicate that Bcl-2 is involved in early stage of tumor development. Ki-67 expression constitutes an independent prognostic factor regarding the outcome of patients with gastric cancer. The positive association between apoptosis and proliferation suggests that apoptosis might reflect not only cell loss but also the proliferative activity. However, further research is required in order to determine if these markers may provide useful information for the prediction of prognosis in patients with colorectal carcinoma.

Oval cell proliferation in cirrhosis in rats. An experimental study.

AIM: Oval cells are liver stem cells involved in liver regeneration following liver damage. Previous studies have shown that pretreatment with a hepatocyte inhibitor is required to allow full oval cell activation. This study investigates whether oval cells develop and proliferate in a model of experimental liver fibrosis without pretreatment with a known hepatocyte inhibitor. METHODS: The study comprised 66 male Wistar rats divided into two groups: A (n = 6): controls; and B (n = 60): CCl(4) injection (intraperitoneally 2 mL/kg bodyweight 1:1 volume in corn oil twice weekly). Rats were sacrificed at four, eight and 12 weeks. Liver tissues were evaluated for the degree of fibrosis (Masson's trichrome), cell proliferation (Ki67 antigen), expression of alpha-fetoprotein (AFP) mRNA (RT-PCR and in situ hybridization), AFP protein (Western blot) and cytokeratin-19. Cells with morphologic features of oval cells that were cytokeratin 19 (CK19)+ and AFP mRNA+ were scored in morphometric analysis. RESULTS: Oval cells were present in all 66 specimens; their percentage was higher in group B compared to group A (P < 0.001). AFP mRNA and protein expression increased as fibrosis advanced. Similarly, the numbers of CK19+, AFP mRNA+ and Ki67+ oval cells were higher in advanced fibrosis stages. CONCLUSION: This study demonstrates that oval cells develop and proliferate in a model of experimental liver fibrosis without pretreatment with a known hepatocytic inhibitor. However, further research is warranted in order to identify the exact molecular mechanisms involved in this process.

Potential role of hepatic progenitor cells expression in cases of chronic hepatitis C and their relation to response to therapy: a clinicopathologic study.

BACKGROUND: This study investigates the correlation of hepatic progenitor cells (HPC) expression with treatment response in patients with chronic hepatitis C. DESIGN: The study comprised 77 liver biopsies with chronic hepatitis C (HCV). All patients were PCR-HCV (+) and received antiviral therapy with interferon or pegylated interferon alpha-2b and ribavirin. Twenty-nine patients were assigned as responders (group A), 29 as nonresponders (group B) and 19 as relapsers (group C). Ten normal liver biopsies were used as controls. Liver paraffin sections were subjected (a) to immunohistochemistry using antibodies for cytokeratins 19 (CK19) and 7 (CK7), alpha-fetoprotein (AFP), leukocyte common antigen (LCA) and CD34 antigen (b) to in situ hybridization for AFP mRNA and (c) to immunohistochemistry+in situ hybridization. Results were expressed as % of positive cells following morphometric analysis. RESULTS: HPC expression was present in all 87 specimens. In the control biopsies, rare HPC were detected. In the CH cases and according to AFP mRNA expression, the grade for % HPC expression was: group B: 53.2+/-2.6> group C: 48.37+/-1.8> group A: 31.4+/-1.6 (group A vs B P<0.01, group A vs C P<0.01, group B vs C P>0.05. Double stain revealed that HPC coexpressed CK19/AFP mRNA, CK7/AFP mRNa and AFP protein/AFP mRNA. HPC-percentages were directly correlated with total HAI score (P<0.01), fibrosis stage (P<0.01), and transaminase values (P<0.05). CONCLUSIONS: This study demonstrates that in cases of chronic hepatitis C, the significant association of HPC expression with the severity of disease and more specifically with the response to treatment implies that HPC development and proliferation may provide additional prognostic information and predict prognosis in such cases.