Low Malignant Potential Cancer Research Articles

Local cytokine concentration in patients with non-muscle invasive bladder cancer of low malignant potential and with varying rates of recurrence

Aim. To investigate local concentrations and distribution of cytokines in tumor tissue and perifocal zone in non-muscle invasive bladder cancer of low malignant potential in patients with low and high probability of disease recurrence. Materials and methods. We have studied tumor and perifocal zone fragments of 31 patients with verified non-muscle invasive bladder cancer of low malignant potential and with different probabilities of recurrence. Fifteen (15) patients developed recurrences 6–9 months after combination treatment. The fragments of primary and recurrent tumors were echanically disaggregated and centrifuged at 1500 rpm for 10 minutes. Levels of cytokines interleukin (IL) -1β, -6, -8, -10, -18, tumor necrosis factor α (TNF-α), interferon-γ (Vektor-Best, Russia), and epithelial neutrophil activating peptide 78 (ENA-78) (CXCL-5 chemokine) (Cloud-Clone Corp., USA) were measured in the samples by ELISA. Results were statistically processed using Statistica 13 software (StatSoft Inc., USA), and presented as median and interquartile range – 25th and 75th percentile (Ме [LQ; UQ]).Results. Comparison of cytokine concentrations within the groups showed that the levels of inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6, IL-18) in tumor tissues were higher than in the perifocal zone tissues. This pattern was expected because tumor is the main site of inflammation. Comparison of these indicators between groups showed that in tumor tissues with an unfavorable course of the disease, namely disease recurrence, the levels of almost all inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6) were higher. A similar pattern was observed when comparing the levels of cytokines in the tissues of the perifocal zone. These differences were statistically significant. ENA-78 concentration was not determined in all cases.Conclusion. The data obtained during the study indicates that in patients with unfavorable disease course (recurrence), tumor growth is associated with high expression of proinflammatory cytokines, which can subsequently lead to development of disease recurrence.

BRAF polymorphisms and the risk of ovarian cancer of low malignant potential

Objective The object of this study was to test the hypothesis that BRAF is a low-risk susceptibility gene for low malignant potential (LMP) ovarian cancer. A recent study of the relationship between BRAF polymorphisms and malignant melanoma identified strong linkage disequilibrium across the BRAF gene with one of the three most common haplotypes (haplotype C) having a population attributable risk of approximately 1.6%. We therefore hypothesized that the same BRAF haplotype may confer an increased risk of serous ovarian tumors of low malignant potential. Methods We genotyped 383 cases of LMP ovarian cancer, including 234 of serous histology, and 987 controls for seven SNPs, representative of the most common BRAF gene haplotypes, using MALDI-TOF mass spectrometry. Results Haplotype information was obtained for 369 LMP ovarian cancer cases and 983 healthy controls. None of the haplotypes were found to be associated with risk of LMP ovarian cancer (OR for haplotype C 0.81, 95% CI = 0.54–1.22), or with the risk of serous LMP ovarian cancer (OR for haplotype C 0.90, 95% CI = 0.56–1.45). Conclusion We found no evidence to suggest that BRAF is a low-risk LMP ovarian cancer susceptibility gene.

Intra-mammary lymph node metastases in an early stage ovarian cancer of low malignant potential

Ž . Low malignant potential LMP tumors of the ovary are usually associated with an excellent prognosis, due, in part, to their early stage at diagnosis. Approximately 50% of LMP tumors are stage I at presentation compared to only 10% of frankly malignant ovarian epithelial cancers. Both LMP and frankly malignant ovarian cancer rarely present with disease outside of the abdominal cavity. We have reported a case of an apparent stage I ovarian LMP tumor with early intramammary lymph node metastases. A 30-year-old female was found to have bilateral adnexal masses upon physical examination during the work-up of her primary infertility. There was no significant family history, but her CA 125 was elevated at 200 IUrml. She underwent an exploratory laparotomy in December 1998, which disclosed bilateral ovarian masses. A frozen-section diagnosis was consistent with a mucinous tumor of low malignant poten-

Platinum-Based Chemotherapy for Advanced-Stage Serous Ovarian Carcinoma of Low Malignant Potential

Purpose: To evaluate the effect of platinum-based chemotherapy on tumor response in patients with advanced-stage serous ovarian carcinoma of low malignant potential. Patients and methods: We conducted a retrospective review of hospital records, pathology slides, and office charts of patients identified as having Stage III or IV serous ovarian cancer of low malignant potential. Results: Between November 1979 and April 1993, 21 patients with advanced-stage serous ovarian carcinoma of low malignant potential received platinum-based chemotherapy following initial cytoreductive surgery. The amount of residual disease was recorded in 20 patients; 8 (40%) had macroscopic residual tumor <2 cm in largest diameter, and 12 (60%) had only microscopic disease. Sixteen patients underwent a second-look laparotomy following chemotherapy; 10 (62.5%) had no evidence of disease, 1 (6%) had a partial response, 2 (12.5%) had stable disease, and 3 (19%) had progressive disease. During a mean follow-up of 64 months, only 1 patient had died of disease. She had progressive disease noted at second-look laparotomy. Five of 6 patients who did not have a complete response to initial chemotherapy underwent further therapy with oral etoposide (1), intraperitoneal platinum (2), intraperitoneal mitoxantrone (1), or both (1). The sixth patient received no further therapy. Three of the patients subsequently receiving salvage intraperitoneal therapy underwent a third-look laparotomy. Two had partial responses noted, while the third patient had stable disease. Conclusions: Platinum-based chemotherapy is effective in achieving surgically documented responses in patients with advanced-stage serous ovarian tumors of low malignant potential. The benefit of this therapy in improving survival is unproven.

Peritoneal carcinomatosis from appendiceal cancer: results in 69 patients treated by cytoreductive surgery and intraperitoneal chemotherapy.

Sixty-nine patients presenting over a 10-year period with peritoneal carcinomatosis from appendiceal cancer were treated with cytoreductive surgery combined with intraperitoneal chemotherapy. The three-year survival is 89.5 percent in patients (38/69) with pseudomyxoma peritonei, 34.5 percent in patients (25/69) with cystadenocarcinoma, and 38.1 percent in patients (6/69) with adenocarcinoma (P < 0.01). In this study, a classification of residual disease following the cytoreductive surgery was used. The prognosis of the patients with minimal residual disease was better than that of those with moderate or gross disease, showing a 91.6 percent three-year survival compared with 47.8 percent and 20 percent, respectively (P < 0.01). The patients without lymphatic or hematogenous metastases had a better three-year survival than those with metastases (75.1 percent vs. 28.6 percent; P < 0.01). These findings suggest that peritoneal carcinomatosis from appendiceal cancer can be treated with long-term disease-free survival. The patients with low malignant potential cancer, complete cytoreduction, and no metastases showed the most effective disease control.