Eddie Fernando Candido Murta

Management of ultrasonographic endometrial thickness in postmenopausal asymptomatic women

Immunostaining of stromal CD56 cells in ovarian malignancies

The aim of this study was to evaluate CD56 immunostaining in the stroma of benign and malignant ovarian epithelial neoplasms and associate the CD56 immunostaining with prognostic factors and survival in ovarian cancer. Patients with ovarian epithelial neoplasia (n=77) were studied with a prospective cohort. The CD56 immunostaining was evaluated in the peritumoral stroma. Two groups were evaluated: benign ovarian neoplasms (n=40) and malignant ovarian neoplasms (n=37). Data were recorded for histological type and grade, International Federation of Gynecology and Obstetrics staging, molecular subtype, and lymph node metastases. Fisher's exact test and Kaplan-Meier survival curves were used, with a significance level of ≤0.05. We found greater CD56 stromal immunostaining in malignant neoplasms when compared to the group of benign neoplasms (p=0.00001). There was no significant difference in relation to the prognostic factors and survival. Malignant ovarian neoplasms showed higher stromal CD56 immunostaining. As the prognostic value of natural killer in ovarian cancer is controversial, knowing the specific function of each cell present both in the tumor tissue and systemically may help guide successful immunotherapies in the near future.

Laboratory predictors of survival in ovarian cancer

SUMMARY OBJECTIVE To relate disease-free survival and overall survival with type I and type II ovarian cancer and preoperative laboratory parameters biomarkers. METHODS A retrospective study was carried out based on the collection of data from medical records of patients with ovarian tumors. Kaplan-Mayer curves were drawn based on the statistical analysis of the data and were compared using the Log-rank test. RESULTS Disease-free survival in type I ovarian cancer was significantly higher than in type II (p=0.0013), as well as in those with normal levels of CA-125 (p=0.0243) and with a platelet-lymphocyte ratio (PLR) lower than 200 (p=0.0038). The overall survival of patients with type I ovarian cancer was significantly higher than in patients with type II, as well as in patients with normal CA-125 serum levels (p=0.0039) and those with a preoperative fasting glucose of less than 100 mg/dL. CONCLUSION CA-125 levels may predict greater overall and disease-free survival. PLR < 200 may suggest greater disease-free survival, whereas normal fasting glucose may suggest greater overall survival.

Laboratory parameters as predictors of prognosis in uterine cervical neoplasia

The aims of study were to assess platelet counts, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), RWD (red cells distribution width) and fasting glucose in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer; and to relate these parameters to prognostic factors and survival in cervical cancer. We evaluated the patients with confirmed diagnosis of invasive cervical cancer (n = 102), and CIN (n = 102). Histological type, NLR, PLR, RDW, platelets count, fasting glucose, staging, overall survival (OS), and disease-free survival (DFS) were evaluated. The results of laboratory parameters were assessed by Mann-Whitney test. A receiver operating characteristic (ROC) curve was used to determine the best cut-off values. Survival was verified by the Kaplan-Meyer method followed by the Gehan-Breslow test. Multivariate analysis was performed using Cox regression. The level of significance was less than 0.05. Comparing CIN and invasive malignancies, higher values of NLR, PLR, RDW and fasting glucose were found in cancer patients (p < 0.0001, p = 0.011, p = 0.0153 and p = 0.0096, respectively). In cervical cancer, higher NLR and PLR values were found at stage II to IV when compared to stage I (p = 0.0066 and p = 0.005, respectively). ROC curves were performed. In invasive neoplasms, the cut-off values for NLR and PLR in the comparison between stage I and greater than I were 4 and 165.45, respectively. For survival curves, there was lower OS and DFS in patients with NLR greater than 4 (p = 0.0004 and p = 0.0153, respectively) and PLR greater than 165.45 (p = 0.0319 and p = 0.0362, respectively). After multivariate analysis, only NLR remained as an independent factor in DFS (HR = 6.095, 95 % CI = 1.120-33.177, p = 0.037) and OS (HR = 4.522, 95 % CI = 1.241-16.479, p = 0.022) CONCLUSION: Higher NLR is associated to lower OS and DFS in invasive uterine cervical neoplasia, and can be considered an independent factor of worse prognosis.

Pathways of IFN-alpha Activation in Patients with Cervical Intraepithelial Neoplasia (CIN)

Abstract Objective The aim of the present study was to compare the local and systemic expression of the factors linked to the interferon alpha (IFN-α) activation pathway in different degrees of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods A total of 128 patients with CIN I, CIN II, CIN III and cervical cancer was evaluated. The real-time polymerase chain reaction (RT-PCR) technique was used to evaluate the gene expression of IFNR1, IFNR2, IFN-α, oligoadenylate synthase (2'5′OAS), cytokine signal suppressor 1 (SOCS) 1, SOCS3, signal transducer and transcription activator 1 (STAT1), and IRF9 from 128 biopsies. A total of 46 out of 128 samples were evaluated by flow cytometry for IFNAR1, IFNAR2, STAT1, IRF7 and IFN-α in peripheral blood cells. Results Patients with CIN II and III (63 samples) had a low local expression of IFNR1, but not IFNR2. Patients with some degree of injury showed high expression of SOCS1 and SOCS3. Systemically, patients with CIN II and III (20 samples) had a significant increase in IFNR1, IFNR2, STAT1, IRF7, and IFN-α in helper, cytotoxic T lymphocytes, and in monocytes. Conclusion Patients with high-grade lesions have increased systemic expression of IFN-α and its activation pathways in helper and cytotoxic T lymphocytes, as well as in monocytes due to an exacerbation of the immune response in these patients. This phenomenon is not accompanied by resolution of the lesion due to a defect in the IFN-α activation pathway that revealed by low local IFNAR1 expression and high local expression of SOCS1 and SOCS3.

Blood count and fasting blood glucose level in the assessment of prognosis and survival in advanced cervical cancer

The objective of this study was to verify whether the parameters of the blood count and the fasting glucose level before treatment are related to prognosis and survival in cervical cancer (IIB-IVB staging). Patients with cervical cancer (stages IIB-IVB) were evaluated (n=80). Age, parity, staging, histological grade, histological type, hemoglobin, red blood cells, hematocrit, neutrophil, lymphocyte and platelet counts, red blood cell distribution width, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, fasting glucose levels, overall survival, and disease-free survival were evaluated. The results of laboratory parameters were compared using the Mann-Whitney U test. Receiver operating characteristic curve was used to obtain the area under the curve and determine the best cutoff values for each parameter. Survival was verified by using the Kaplan-Meier method, followed by the log-rank test. The level of significance was ≤0.05. Regarding staging, lower hemoglobin values (p=0.0013), red blood cells (p=0.009), hematocrit (p=0.0016), higher leukocytes (p=0.0432), neutrophils (p=0.0176), platelets (p=0.0140), red blood cell distribution width (RDW) (p=0.0073), neutrophil-lymphocyte ratio (p=0.0039), platelet-lymphocyte ratio (p=0.0006), and fasting glucose level (p=0.0278) were found in IIIA-IVB compared with IIB staging. Shorter disease-free survival was associated with hemoglobin ≤12.3 g/dl (p=0.0491), hematocrit ≤38.5% (p=0.05), neutrophil-lymphocyte ratio >2.9 (p=0.0478), and platelet-lymphocyte ratio >184.9 (p=0.0207). Shorter overall survival was associated with hemoglobin ≤12.3 g/dl (p=0.0131), hematocrit ≤38.5% (p=0.0376), neutrophil-lymphocyte ratio >2.9 (p=0.0258), and platelet-lymphocyte ratio >184.9 (p=0.0038). The analysis of these low-cost and easily accessible parameters could be a way to monitor patients in order to predict treatment failures and act as early as possible.

Evaluation of cytokine immunostaining in ovarian neoplasms and endometriomas

The objective of our study was to quantify and compare the immunostaining of IL-2, IL-5, IL-6, IL-8, and TNF-α in endometriomal tissue, non-neoplastic tumors, benign neoplasms, and malignant ovarian neoplasms. The study involved 90 patients: 15 non-neoplastic ovarian lesions, 28 ovarian benign neoplasms, 28 ovarian malignant neoplasms, and 19 ovarian endometriomas were diagnosed. Immunohistochemistry was performed for cytokines IL-2, IL-5, IL-6, IL-8, and TNF-α and their concentrations were compared in these groups. Fisher's exact test was used, requiring a P-value of < 0.05 for significance. IL-5 and IL-8 epithelial immunostaining is stronger in endometriomas than in ovarian cancer (P-values of 0.0046 and 0.0149, resp.). The stromal immunostaining of TNF-α, IL-5, IL-6, and IL8 is stronger in endometriomas than in ovarian cancer (P-values of 0.0008, < 0.0001, 0.0003, and 0.0006, resp.). Stronger immunostaining of some cytokines in endometriomas compared to ovarian cancer reflects an inflammatory and immune response that could be future targets for new discoveries about the infiltrative behavior of endometriosis.

Endometrioid adenocarcinoma with sacral metastasis

Most bone tumors are metastatic. Breasts, lungs, kidneys, and thyroid are the primary sites most commonly involved in bone metastasis-type outcomes. This case study describes the involvement of a patient with a bone tumor located in the axial skeleton, initially in the sacral region. However, the primary site was undefined. Therefore, it was necessary to expand the investigation with immunohistochemistry, which demonstrated a metastatic tumor compatible with endometrioid adenocarcinoma. But even after examination, no active lesion was found in the endometrial region. The study was observational, descriptive, and aimed to discuss the importance of more specific investigative methods. In this context, immunohistochemistry stands out as an exquisite method capable of optimizing diagnosis, therapy, and consequently, prognosis. Key words: bone neoplasm – endometrioid adenocarcinoma – immunohistochemistry

Peritumoral stroma and systemic inflammatory response in cervical cancer

Objective: To compare cervical stroma in advanced cervical cancer with the control group; to compare, in the pre-treatment period, hemogram parameters in patients with advanced cervical cancer with the same parameters as the control group; and to verify if there is an association of stromal markers with prognostic factors in cervical cancer. Materials and methods: We prospectively evaluated 16 patients diagnosed with advanced invasive cervical cancer. A control group of 22 patients was used (uterine leiomyoma). Immunohistochemistry was performed to verify the stromal immunostaining of alpha-smooth muscle actin (SMA) and fibroblast activation protein alpha (FAP). Immunostainings and hemogram parameters were compared using Fisher's exact and Mann-Whitney Test, respectively. Results: Strong FAP immunostaining was more frequent in patients with cervical cancer when compared with patients with leiomyoma (P = 0.0002). Regarding SMA, strong immunostaining was also found more in the group of cancer patients compared to the control group (P &lt; 0.00001). The neutrophil-lymphocyte ratio (NLR) values were higher in the cancer patient group compared to the control group (P = 0.0019). There was no association of the parameters studied with prognostic factors. Conclusions: Strong FAP and SMA immunostaining was found more in patients with cervical cancer when compared to the control group. NLR values were also higher in cervical cancer. Key words: uterine cervical neoplasms – alpha-smooth muscle actin – fibroblast activation protein alpha – blood cell count