Association of CD133, ALDH1, CD117 and OCT4 expression with prognosis of patients with cervical cancer.

Cancer stem cells (CSC), a small population of neoplastic cells, are associated with worse prognosis. The aim of this study was to evaluate the expression of ALDH1, CD117, CD133 and OCT4; potential markers of CSC; and their associations with the prognosis of women diagnosed with cervical cancer. This retrospective cohort study included 126 women diagnosed with cervical cancer whose biopsies were analyzed by immunohistochemistry. Median values of marked cells were used to define cutoff points for low and high expression. For specific survival, multivariate analyses showed statistical significance for lymph node metastases (HR 8.15; 95% CI 3.00-22.18) and borderline significance for high CD133 expression (p = 0.058). For overall survival, multivariate analyses showed statistical significance for IIA-IVB staging (HR 4.60; 95% CI 1.46-14.56), lymph node metastases (HR 5.13; 95% CI 12.02-13.03) and high CD133 expression (2.67; 95% CI 1.11-6.43). Considering only women with SCC, the same clinicopathological variables were associated with worse specific and overall survival in univariate analyses. However, higher expression of CD 133 (HR 11.10; 95% CI 2.42-50.94 and 6.00; 95% CI 2.02-17.87) and staging IIA-IVB (HR 5.96; 95% CI 1.30-27.34 and HR 12.47; 95% CI 2.45-63.54) respectively impacted negatively specific and overall survival, as multivariate analyses showed. Secondarily, it was observed that ALDH1 expression was associated with adenocarcinoma and CD117 expression with squamous cells carcinoma. Higher expression of CD133 was associated with worse specific and overall survival, indicating that it could have relevance as a clinical marker and therapeutic target.

Angiogenesis pattern and H3.3 histone mutation in aggressive and non-aggressive central giant cell lesions.

OBJECTIVE: The aim of this study was to evaluate angiogenesis in central giant cell lesions (CGCL) and its association with biological behavior. In addition, investigation of the histone H3.3 mutation was performed. DESIGN: Thirty-eight cases of CGCL were classified as aggressive (n = 9) or nonaggressive (n = 29). Cases were submitted to immunohistochemistry to compare angiogenesis using Wilms' tumor protein 1 (WT1), platelet endothelial cell adhesion molecule (CD31) and endoglin (CD105) between groups. To verify the presence of genic mutation, histone H3.3 was investigated. RESULTS: WT1 was expressed in mononuclear and giant cells of all cases. CD31 and CD105 were expressed in CGCL microvessels, with a higher CD105 microvascular density than CD31. No statistically significant difference was observed between groups. None of the cases studied showed the histone mutation. CONCLUSIONS: There was no difference between aggressive and nonaggressive lesions regarding the angiogenic markers. The expression of WT1 and CD105 suggests that CGCL presents a tumoral vascular pattern with high neoangiogenic activity. The absence of histone mutation may indicate that CGCL is not a true giant cell tumor.

Immune microenvironment and evasion mechanisms in adenoid cystic carcinomas of salivary glands.

OBJECTIVES: The objective of the present study was to investigate the expression of immune checkpoints (PD-L1, PD-L2, PD-1 and CTLA-4), immune inhibitory molecule HLA-G, markers of tumor-infiltrating lymphocytes (TIL) and dendritic cells (DC), as well as its association with clinicopathological features of adenoid cystic carcinomas (ACC) of the salivary glands. MATERIALS AND METHODS: Thirty-six samples from patients with ACC were analyzed immunohistochemically for the expression of PD-L1, PD-L2, PD-1, CTLA-4, HLA-G, CD8, GrB, CD1a and CD83. Positivity of HLA-G, PD-L1 and PD-L2 expression was defined by cut-offs values. CD8+ TIL was measured semiquantitatively and also using cut-off values obtained by the ROC curve considering recurrence of the lesion. RESULTS: ACC showed low CD8+, GrB+  TIL, CD1a and CD83 populations, as well as scarce positivity for CTLA-4 and PD-1. In contrast, PD-L2 and HLA-G expression was increased, while no PD-L1 expression was detected. Interestingly, cases with lower CD8+ TIL density presented greater recurrence rates. CONCLUSION: Our findings suggest that the ACC microenvironment exhibits low immunogenicity, represented by low TIL and DC density. Moreover, there seems to be activation of the immune inhibitory proteins/PD-L2 and HLA-G, a scenario that may favor tumor escape from the immune system and partially explain the poor prognosis of ACC.

Evaluation of HLA-G, HLA-E, and PD-L1 proteins in oral osteosarcomas.

OBJECTIVE: The aim of this study was to investigate the expression of human leukocyte antigens (HLAs) G and E and programmed death-ligand 1 (PD-L1) in oral osteosarcoma (OO) (n = 13). The relationship between the expression of these molecules and histologic grading and metastasis was also evaluated. STUDY DESIGN: HLA-G, HLA-E, and PD-L1 were identified by immunohistochemistry. Samples of normal bone tissue (n = 6) were used as controls. The sections were evaluated using a semiquantitative scoring system with an immunoreactive score, where a score of 0 was considered absent, ≤2 was low, and >2 was high expression. RESULTS: We identified high expression of HLA-G, HLA-E, and PD-L1 by malignant osteoblastic cells in 69.2% of OO cases, which was statistically higher than that in controls (P < .05). Overexpression of these proteins was identified in 8 of 11 samples of high-grade and 1 of 2 samples of low-grade OO. Additionally, 66.6% of patients with metastases (n = 4) and 71.4% of patients without metastases (n = 5) had high expression of HLA-G, HLA-E, and PD-L1 in tumor samples (P > .05). CONCLUSION: OO had high expression of HLA-G, HLA-E, and PD-L1 irrespective of clinicopathologic parameters, including histologic grading and metastasis.

Dealing with bone marrow biopsies in the staging of classical Hodgkin lymphoma: an old issue revisited in the (18)F-fluorodeoxyglucose-positron emission tomography era.

Bone marrow biopsy is recommended for staging of classical Hodgkin lymphoma. The aim of this study was to compare bone marrow evaluation by histology with that obtained by (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET). One hundred and three cases of Classical Hodgkin Lymphoma were reviewed. All patients were submitted to FDG-PET evaluation. Bone marrow biopsy results were compared with clinical data and FDG-PET results. Ninety-one cases had available bone marrow biopsies. Overall, there were 16 positive and one suspect case. In five cases, the FDG-PET scan was positive and biopsy was negative: 1/5 was found to correspond to a bone fracture, 3/5 showed marked reactive bone marrow changes and in 1/5 no explanation for the discrepancy was found. FDG-PET showed high sensitivity, supporting the idea that when it is negative, biopsy could be avoided. Care should be taken in patients with a positive FDG-PET, where confirmation by bone marrow biopsy should be recommended.

Response to dasatinib in a patient with concomitant chronic myeloid leukemia and chronic lymphocytic leukemia.

While chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) are common diseases in the elderly, they rarely occur simultaneously in the same patient. Here we present the case of a 77-year-old patient diagnosed with CML in the chronic phase who showed an optimal response to 400 mg/day of imatinib. This patient progressed to Binet B-CLL with an 11q22.3 deletion and CD38 positivity in the 4th month of treatment. During the follow-up, his lymphocyte number doubled in <6 months. Based on previous reports, dasatinib was chosen instead of imatinib. After 6 months of treatment with 100 mg/day of dasatinib, the patient demonstrated a partial response, characterized by the regression of lymph node enlargement, a hemoglobin level of 10.7 g/dl, neutrophils of 1.7 × 10(9)/l, a 82% reduction in the lymphocyte number and an increase in cytotoxic CD8+ and large granular lymphocytes. This partial response has persisted to the present time. While little data have been published regarding the in vitro effect of dasatinib monotherapy for CLL, this case report provides some evidence of the clinical activity of dasatinib in CLL.