Stromal IL2 is related to the neutrophil/lymphocyte ratio in epithelial ovarian cancer.

INTRODUCTION: There is a need for the development of new biomarkers for diagnosis and prognosis of ovarian cancer, which can ideally serve as targets for new therapeutic modalities and individualization of treatment. The objectives of this study were to determine the prognostic significance of the neutrophil/lymphocyte ratio in the peripheral blood of patients with ovarian cancer and tumor staging, and to associate this marker with the immune expression of a panel of cytokines. METHODS: The study included 24 patients with malignant ovarian neoplasia treated at the Pelvic Mass Outpatient Clinic of the Clinical Hospital of the Federal University of Triângulo Mineiro. The neutrophil/lymphocyte ratio was calculated as the absolute number of neutrophils divided by the absolute number of lymphocytes. Expression of the cytokines was evaluated by the immunohistochemistry method (IL2, IL5, IL6, IL8, IL10 and TNF-R1). Fisher's statistical test was used for the comparisons of immunohistochemical expression with the neutrophil/lymphocyte ratio, and the unpaired T-Test was used in the analysis of the association of this ratio with tumor staging. RESULTS: A neutrophil/lymphocyte ratio > 2.6 was significantly higher in the more advanced stages (II-IV) of malignant ovarian neoplasia (p = 0.0098). In addition, this ratio > 2.6 was associated with IL2 stromal immunostaining (1-3) (p = 0.0472). CONCLUSION: Stromal IL-2 is associated with higher a neutrophil/lymphocyte ratio, suggesting a worse prognosis in ovarian cancer and its role in tumor immunology; a neutrophil/lymphocyte ratio > 2.6 is associated with more advanced stages of malignant ovarian neoplasia.

Role of Intracystic Cytokines and Nitric Oxide in Ovarian Neoplasms.

The development of new biomarkers for the diagnosis and prognosis of ovarian cancer may provide an opportunity for new therapies. In this study, we aimed to compare cytokines (interleukin [IL]-2, IL-5, IL-6, IL-8, IL-10 and tumour necrosis factor [TNF]-α) and nitric oxide (NO) metabolite levels in non-neoplastic tumours, benign primary ovarian tumours and malignant primary ovarian neoplasms. The secondary aim was to relate cytokine and intracystic NO metabolite levels to clinical, laboratory and pathologic characteristics for patients with primary ovarian malignancies. We evaluated 110 patients with adnexal masses. Cytokine concentrations were quantified by enzyme-linked immunosorbent assay and nitrate concentrations by enzymatic reduction of nitrite by nitrate reductase. Patients with malignant neoplasms had higher IL-6, IL-8 and NO levels compared to patients with benign neoplasms. Histologic grade 1 tumours were associated with elevated IL-2 levels, whereas anaemia was associated with elevated IL-6 levels. On average, those patients with elevated IL-8 levels also had a neutrophil/lymphocyte ratio (NLR) greater than 2.6 and less than 36 months of disease-free survival (DFS). Patients with normal CA 19-9 levels had elevated IL-10 levels. TNF-α was elevated in patients with two carcinogenesis and those with a platelet/lymphocyte ratio (PLR) less than 300. NO levels were higher in patients with an NLR less than 2.6 and CA 19-9 greater than 35 U/ml. Elevated intracystic cytokine levels, especially IL-6 and IL-8, are associated with worse prognosis in ovarian cancer.

Parameters of blood count and tumor markers: a retrospective analysis and relation to prognostic factors in ovarian cancer.

PURPOSE OF INVESTIGATION: The aims of study were to evaluate potential prognostic laboratory factors in ovarian cancer (blood count parameters and tumor markers) and to relate these parameters with prognostic factors. MATERIALS AND METHODS: The authors evaluated patients that underwent surgical treatment and with confirmed histopathologic diagnosis of ovarian cancer. Age, FIGO stage, type of surgery, serum levels of tumor markers, parameters of blood count, disease-free and overall survival were recorded. Mann-Whitney test was performed. The significance level was less than 0.05. RESULTS: Higher levels of CA 125, CA 15.3, and platelets were found in the group with Stage hII/I, since hemoglobin levels were higher in stage I/II (p < 0.05). CEA levels were higher in the group of non-serous neoplasms (p < 0.05). Higher levels of CA125, CAIl5.3 and platelets were seen in the group histological grade 2/3 (p < 0.05). CONCLUSION: CA 125, CA 15.3, hemoglobin, and platelets can be related prognostic factors in ovarian cancer.

The immune response in malignant ovarian neoplasms.

The objective of this study was to review studies that have investigated the immune response in the presence of a malignant ovarian neoplasia. A review of the literature was performed to identify studies of malignant ovarian neoplasia, particularly studies that addressed the potential for cytokines, nitric oxide, and lymphocytes to mediate an immune response against ovarian cancer. Certain subsets of tumor-infiltrating leukocytes and/or tumor-associated leukocytes have been found to correlate with an improved disease prognosis, while other lymphocyte subsets (such as CD3+/CD4+/CD25+ T cells) have been associated with a poor prognosis. These data suggest that cytokines can have a protective role, or can promote an immune system defense against a cancer. In particular, certain cytokines (e.g., IL 8, IL 10) represent attractive candidates for the development of new diagnostic, prognostic, and therapeutic strategies for the treatment of ovarian cancer.

Frequency of endometriosis and adenomyosis in patients with leiomyomas, gynecologic premalignant, and malignant neoplasias.

OBJECTIVE: This study investigated the association between gynecological neoplasms, endometriosis, and adenomyosis in women who underwent surgical treatment for gynecological cancer and uterine leiomyoma during reproductive years or after menopause. MATERIALS AND METHODS: Information was collected from patient records from the Hospital's database from 1985 to 2007. The study included 502 women, of which 375 were premenopausal and 132 were postmenopausal. RESULTS: A significant association was observed between the occurrence of adenomyosis in cancer in women with four or more pregnancies, and in women aged over 40 years (p < 0.0001). The frequency of adenomyosis was significantly higher than the frequency of endometriosis for cancer in two sites (p = 0.0419) or for leiomyomas (p < 0.0001). CONCLUSION: Therefore adenomyosis is more frequently found than endometriosis in women with leiomyomas or cancer in two sites in premenopausal women, and clinicians need to be aware of patients with adenomyosis and the risk of cancer.

Loss of heterozygosity in the fragile histidine triad (FHIT) locus and expression analysis of FHIT protein in patients with breast disorders.

PURPOSE OF INVESTIGATION: The fragile histidine triad (FHIT) gene is a tumor suppressor frequently inactivated in various types of tumors. The authors evaluated the occurrence of loss of heterozygosity (LOH) in the FHIT locus and FHIT protein changes in breast tissue. MATERIALS AND METHODS: Blood and breast tissue samples were obtained from 35 women with mammary disorders. The occurrence of LOH in FHIT locus was assayed by polymerase chain reaction (PCR), and the results obtained from blood and breast tissues from each patient were compared. FHIT protein expression was evaluated by immunohistochemistry. RESULTS: LOH in the FHIT gene occurred in 48.6% (17/35) of patients with mammary disorder. Among patients with malignant breast disorders, 59.1% (13/22) presented LOH in the FHIT gene in comparison with patients with benign breast lumps, in which the LOH was observed in 30.8% (4/13) of women, suggesting that changes in this gene occur prior to the process of mammary carcinogenesis. The changes in the locus of the FHIT gene occur with greater frequency in the coded region of the gene, principally near exons 5 and 8, where the FRA3B site and the histidine triad respectively are found. Changes in FHIT did not modify protein expression. The association between menopause and LOH in the FHIT gene was evident. CONCLUSIONS: LOH in the FHIT gene may be related to menopause in women with breast disorders.

Frequency of recurrence after surgical treatment of cervical intraepithelial neoplasia grade 1-3.

PURPOSE OF INVESTIGATION: The objective was to demonstrate the frequency of invasive cervical cancer or recurrent CIN in patients treated by a previous diagnosis of CIN 1-3. METHODS: We analyzed 1,397 records colpocytologic and medical records. Recurrence of CIN or invasive neoplasia of the cervix after treatment of CIN was assessed. The chi-square test was used for statistical analysis (significance level set at less than 0.05). RESULTS: We obtained 696 CIN 1, 244 CIN 2, 451 CIN 3, and six squamous carcinoma. Regarding patients who relapsed, there were 6/690 (0.9%) patients had an initial diagnosis of CIN 1, 8/236 (3.4%) CIN 2 and 21/430 (4.9%) CIN 3 (p < 0.0001). Comparing the frequency of relapse among each group, we found: CIN 1 vs CIN 2: p = 0.0073; CIN 1 vs CIN 3: p < 0.0001; CIN 2 vs CIN 3: p = 0.38. CONCLUSION: Although the number of relapses when comparing CIN 2 and CIN 3 were not significant, the data suggest that CIN 2 has lower recurrence rates, so these patients require more conservative treatment if a desire of future pregnancy is expressed.

Myofibroblastic inflammatory breast tumor and fibrosarcoma: a case report.

Myofibroblastic inflammatory tumors can occur in any human tissue. They are benign lesions and more common in young patients. We describe the case of a 41-year-old patient with a nodule measuring 2.5 x 1.5 cm in the superior lateral quadrant of the left breast. The pathological examination showed proliferation of the spindle cells in dense fascicles interspersed by colagen among frequent plasmocytes, lymphocytes and eosinophils, associated with scarce typical mitosis. In the same site ten years before the patient had undergone a nodulectomy and the diagnosis was a benign filloid tumor. The patient returned with a nodule in the surgical scar at follow-up and the incisional biopsy showed a malignant filloid tumor with a sarcomatous component. A mastectomy was performed.

Gynecological malignant neoplasias diagnosed after hysterectomy performed for leiomyoma in a university hospital.

PURPOSE: To analyze the findings of malignant neoplasms after hysterectomy for benign conditions. METHODS: A retrospective study from January 1987 to December 2008 was conducted. We analyzed all simple hysterectomies with or without salpingo-oophorectomy for benign conditions (leiomyoma). Incomplete dossiers of patients or cases with uncertain clinical diagnostics were excluded. We analyzed histopathological results, age, parity, indications for hysterectomies with or without salpingo-oophorectomy, stage (if malignant) and therapy. RESULTS: 2,016 hysterectomies with or without salpingo-oophorectomy were performed. Of 2,016, 652 (32.3%) had had a previous diagnosis of malignancy and 1,364 (67.7%) had had a clinical diagnosis of benignancy (leiomyoma). From the total of 1,364, three (0.22%) cases of cancer were diagnosed after anatomopathological study of the uterine specimen, two sarcomas and one endometrial cancer. No cases of incidental ovarian or uterine cervical cancer were diagnosed. CONCLUSIONS: Gynecological malignances in surgical specimens of patients submitted to surgery (hysterectomy and/or salpingo-oophorectomy) for benign conditions are rarely found.

Frequency of cervical intraepithelial neoplasia and infectious agents for vaginitis in menstrual cycle phase.

OBJECTIVE: The study objective was to verify differences in the diagnosis of infectious agents and CIN in cytological smears in the proliferative and secretory phases of the menstrual cycle. METHODS: A retrospective study was carried out at the Federal University of "Triângulo Mineiro". Presence of Candida albicans, Trichomonas vaginalis, clue cells, Doderlein bacilli, cytolytic flora, coccoid bacillus, CIN and HPV were collected from the vaginal cytology tests, cervical and endocervical in healthy women of reproductive age from 1994 to 2004 (about 14,000 in total). The cytologies were divided into two groups: proliferative and secretory phase. Chi-square and Fisher's exact tests were used for statistical analysis with the significance level set at less than 0.05. RESULTS: The frequency of cytolysis and candidiasis was higher in the secretory phase of the menstrual cycle (p < 0.0001). When the presence of CIN associated with vulvovaginitis was evaluated, there was no significant difference in cytologies with CIN between the first and the second phases of the menstrual cycle. CONCLUSION: Frequency of the cytolytic flora and Candida albicans is influenced by the phase of the menstrual cycle, but CIN is not.

Ovarian clear cell carcinoma associated with endometriosis: a case report with immunohistochemical study.

Endometriosis is a frequent benign gynecological disease; nonetheless, it can demonstrate some aspects that resemble malignant disease. Malignant transformation of endometriosis occurs mainly in the ovary. A rare case of transition between typical endometriosis and clear cell carcinoma with immunohistochemical study is presented. The patient, a 30-year-old Caucasian woman (para 0), was diagnosed with endometriosis ten years before. Six months later she developed a left cystic ovarian tumor (58 cm3) that persisted after two ultrasounds in a four-month period. Tumor markers were normal (CA125, CA 15.3, CA 19.9, alpha-fetoprotein, carcinoembrionary antigen A1). There was no ascites. The left ovarian mass was removed by laparotomy and endometriosis in continuity with carcinoma positive for cytokeratin 7 and estrogen receptor was revealed. CD10 was positive in the stromal cells of the endometriosis. Clear cell carcinoma grade 3 was diagnosed. In conclusion, although a rare event, the association of typical endometriosis and clear cell carcinoma of the ovary should be kept in mind, mainly in patients with a persistent ovarian cyst.

Androgenic juvenile granulosa cell tumor of the ovary with cystic presentation: a case report.

Granulosa cell tumors account for approximately 1-2% of all ovarian tumors. There are two types: adult granulosa cell tumor and juvenile granulosa cell tumor. Juvenile granulosa cell tumors constitute 5% of this histological subtype, and the prognosis is good because the majority present as Stage I tumors. The treatment can consist of conservative surgery. Androgen production is rare and produces virilization in women. These tumors are usually solid or predominantly solid. We describe the case of a 13-year-old girl with androgenic manifestations and increased abdominal size. Her plasma testosterone level was elevated. A left adnexal cyst (14.4 x 9.1 x 9.7 cm) was revealed at pelvic ultrasonography. The patient underwent an exploratory laparotomy, revealing a left ovarian cystic tumor. Diagnosis was juvenile granulosa cell tumor.

Choriocarcinoma complicated by a vaginal fistula, sepsis and hemorrhagic shock. Case report.

A case of poor prognostic choriocarcinoma developing sepsis is described. The patient was treated with vaginal drainage of pelvic abscess metastases, bilateral hypogastric artery ligation to prevent hemorrhage and single-agent chemotherapy.