Distribution of CXCR4 and tumour-infiltrating lymphocytes in breast cancer subtypes; their relationship with each other, axillary lymph node involvement, and other prognostic indicators.

We have investigated the distribution of chemokine receptor 4 (CXCR4) and CD8-positive, tumour-infiltrating T lymphocytes (CD8+ TILs) in breast cancer subtypes and explored the relationship between them and the well-established conventional prognostic markers, including axillary lymph node involvement. A total of 250 breast cancer patients were included in the study. The patients were separated into luminal A+B, HER2 enriched/overexpressed (HER2+), and triple- negative, on the basis of their staining characteristics, via conventional staining methods. Immunohistochemical (IHC) staining for CXCR4 and CD8+ TILs were performed on the archival tissues from each patient. With increasing intensity of CXCR4 staining, there was a higher incidence of lymph node metastasis (p < 0.01). Similarly, there was a positive correlation between the primary tumour size, HER2+ subtype, lymphovascular invasion, and axillary lymph node involvement. Dense lymphocytic infiltration was observed in HER2+ and triple-negative patients. No correlation between CD8+ TILs in all sites and breast cancer subtypes was discovered. A reverse correlation was discovered with CD8+ TILs stained only intratumorally and CXCR4 expression. In conclusion, lymph node involvement correlates with higher CXCR4 expression in all breast cancer subtypes. Conversely, no such correlation is found with CD8+ TILs.

CXCR-4 and COX-2 expression in basal cell carcinomas and well-differentiated squamous cell carcinomas of the skin; their relationship with tumor invasiveness and histological subtype.

OBJECTIVE: Both CXCR-4 and COX-2 are biological markers that play a significant role in several neoplastic processes. We explored the differences in expression of these markers in certain subtypes of basal cell carcinoma, and squamous cell carcinomas in general. MATERIAL AND METHOD: In this study, we investigated the differences between 38 patients with basal cell carcinoma (nodular, infiltrative and micro-nodular subtypes) and 24 patients with well-differentiated squamous cell carcinomas with respect to their depth of invasion, tumor location, age, and CXCR-4 and COX-2 expression. RESULTS: Statistically, we found no significant difference between squamous cell carcinomas and basal cell carcinoma in terms of CXCR-4 and COX-2 expression; however, the degree of marker expression became stronger with increasing depth of invasion in both tumors. The expression of both markers was also higher in infiltrative type basal cell carcinoma compared to all the other subtypes. The results were statistically significant (p<0.05). Additionally, a significantly positive correlation also existed between COX2 and CXCR4 expression (p < 0.05). CONCLUSION: The degree of expression of CXCR-4 and COX-2 is related to invasiveness in both malignancies; thus, infiltrative type of basal cell carcinoma displays the highest degree of CXCR-4 and COX-2 expression among all the subtypes. Furthermore, our results indicate that these two biological markers may both be involved in the process of carcinogenesis and require investigation with further molecular and genetic studies in larger series.

[Familial Mediterranean fever with pulmonary manifestations alone; early diagnosis with genetic analysis]. / Yalniz pulmoner bulgulari olan ailesel Akdeniz atesi; genetik analizle erken tani

Painful pleural effusion and fever are the only presenting clinical features in 5-10% of patients with familial Mediterranean fever (FMF). We report the results of genetic analysis that have confirmed the diagnosis of FMF in six patients who presented with fever and pleuritic pain alone. At time of presentation, all six patients received antibiotic treatment for suspected infectious etiology following routine laboratory and microbiologic evaluation. Gene analysis was performed when other diagnostic studies had failed to uncover the etiology and patients did not respond to conventional treatment. Mutation analysis for MEFV gene performed from genomic DNA by the direct DNA sequence method. Half of the patients were male. Five were older than 50, one was 33 years old. All of the patients had fever and pleuritic pain; none had the typical abdominal symptoms. Erythrocyte sedimentation rates and C-reactive protein levels were high. Pericardial effusion was discovered in three patients. Genetic analysis confirmed; R202Q/R202R, E148V/E148E, R314R, E474E, Q476Q, D510D, E148Q/E148E heterozygote polymorphisms with and M694V/M694V mutations were determined on the MEFV gene. In five patients an improvement has been observed with colchicine therapy. In one patient steroid treatment was needed because of no response to colchicine and clinical deterioration. Rapid improvement was observed in this case with steroid therapy. But after cessation of steroid therapy new flare developed that responded to new colchicine therapy. In patients who present with pleuritic chest pain and fever without an identifiable etiology, genetic analysis help making the diagnosis of FMF, especially in certain ethnic populations where FMF is relevant. This should help patients receive specific treatment without unnecessary delay. Thus, by making early diagnosis and timely delivery of treatment, disease progression is delayed and development of secondary amyloidosis avoided.

A prospective, multicentre clinical trial comparing cisplatin plus gemcitabine with cisplatin plus etoposide in patients with locally advanced and metastatic non-small cell lung cancer.

OBJECTIVE: Cisplatin-gemcitabine (PG) and cisplatin-etoposide (PE) combinations are active regimens for non-small cell lung cancer (NSCLC). The present study aimed to compare PG with PE in the treatment of patients with stage IIIB and IV NSCLC. METHODOLOGY: We conducted a prospective, multicentre trial. A total of 166 patients were enrolled into the study and received either gemcitabine (1,000 mg/m(2)) on days 1, 8 and 15 plus cisplatin (80 mg/m(2)) on day 2 every 4 weeks, or etoposide (100 mg/m(2)) on days 1, 2 and 3 plus cisplatin (80 mg/m(2)) on day 1 every 3 weeks. RESULTS: The overall response rate was superior in the PG group (54.8%vs 39.0%, P=0.045). There was no significant difference in survival between the two groups, with respective median and 1-year survival of 38 weeks and 33.3% for the PG group, and 34 weeks and 23.2% for the PE group. There was also no statistical difference for time to progression between the two groups. Neutropenia and thrombocytopenia were seen more frequently in the PG group (grade 3 neutropenia, 33.3%vs 15.9%, P=0.012; grade 3 thrombocytopenia, 27.4%vs 3.7%, P<0.001 and grade 4 thrombocytopenia, 10.7%vs 1.2%, P=0.018). CONCLUSION: PG is an active chemotherapy regimen and has a better response rate than PE in advanced NSCLC, although there was no difference in time to progression and overall survival. A higher incidence of haematological toxicity was seen with PG than with PE.

Gemcitabine and vinorelbine combination in patients with metastatic breast cancer.

Both gemcitabine and vinorelbine as single agents have significant activity against metastatic breast cancer, with an overall response rate ranging from 14% to 40%. Because each drug has different mechanisms of action and toxicity profile, we have evaluated the activity and tolerability as a combined regimen in metastatic breast cancer patients. Thirty-two breast cancer patients with prior chemotherapy for metastatic disease received a combination of gemcitabine and vinorelbine at 1,200 and 30 mg/m2, respectively. The drugs were administered on days 1 and 8 of every 21-day cycle. The study was designed to evaluate the response rate, the duration of response, the time to progression, and overall survival. Toxicity and tolerability of this combination were also evaluated. Out of 32 patients analyzed, a complete response was achieved in 2 patients (6.3%) and a partial response in 12 patients (37.5%), with an overall response rate of 43.8%. After a median follow-up of 7 months, the median duration of response was 5.3 months, and the time to progression was 5.0 months. Overall survival was not reached because the majority of the patients were alive at the time of analysis. The gemcitabine and vinorelbine combination was tolerable, with hematologic toxicity being the most common side-effect. Three patients suffered from grade 4 neutropenia, and none suffered from grade 4 thrombocytopenia. Nonhematologic toxicity was minimal and transient, with nausea and phlebitis being the most common. The gemcitabine and vinorelbine combination at the previously specified doses shows significant activity in metastatic breast cancer patients. The treatment is well tolerated and has an acceptable toxicity profile. In patients previously treated with anthracyclines and taxanes, this combination regimen offers an alternative treatment with preservation of a good quality of life.