PD-L1 protein expression and copy number gains in HIV-positive locally advanced cervical cancer.

BACKGROUND: The programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) axis may represent a target for cervical cancer; however, it is poorly understood in human immunodeficiency virus (HIV)-infected patients. METHODS: We evaluated HIV-positive (n = 42) and HIV-negative (n = 110) women with locally advanced cervical cancer regarding their PD-L1 expression, determined by combined positive score (CPS) ⩾ 1 and tumor proportion score (TPS) ⩾ 25%, and PD-L1 copy number alterations, assessed by fluorescence in situ hybridization. RESULTS: Regardless of HIV status, 84.9% and 44.8% of cases were PD-L1-positive according to CPS ⩾ 1 and TPS ⩾ 25%. Per CPS ⩾ 1, PD-L1 positive rate was similar between HIV-positive and HIV-negative women, whereas a significant difference was seen per TPS ⩾ 25%. Tumor size and parametrial invasion were correlated with PD-L1 positivity in HIV-negative women, whereas anti-retroviral therapy (ART) was correlated with TPS < 25%. Low CD4-positive cell counts were associated with CPS < 1 in HIV-positive women. No significant difference was observed in PD-L1 copy number status between HIV-positive and HIV-negative women. PD-L1 amplification and polysomy were independently associated with TPS ⩾ 25%, whereas the presence of parametrial invasion was independently associated with CPS ⩾ 1. Cancer stage and PD-L1 amplification were identified as independent predictors of recurrence-free survival [hazard ratio (HR) = 2.40 (1.32-4.36) and HR = 5.33 (1.94-14.61)] and cancer-specific survival [HR = 13.62 (5.1-36.38) and HR = 3.53 (1.43-8.69)]. PD-L1 polysomy was an independent predictor of locoregional recurrence-free survival [HR = 3.27 (1.27-8.41)]. HIV status and PD-L1 expression (CPS ⩾ 1 or TPS ⩾ 25%) were not associated with poor patient outcomes. CONCLUSION: PD-L1 amplification and polysomy are the strongest drivers of PD-L1 expression in cervical cancer, and could represent prognostic biomarkers for anti-PD-1/PD-L1 therapy. Cervical cancer biology may be modulated by HIV infection, CD4-positive cells, and HIV treatments.

Expression of CD24 in cholangiocarcinoma cells is associated with disease progression and reduced patient survival.

Cholangiocarcinoma is frequently found to invade local tissues and metastasize to distal organs. We investigated the expression of CD24 in cholangiocarcinoma samples and its prognostic significance. In addition, the cellular function of CD24 was studied in the RMCCA1 cholangiocarcinoma cell line. High CD24 expression significantly correlated with lymph node metastasis and positive surgical margins in cholangiocarcinoma patients. Univariate and multivariate analyses further demonstrated that CD24 expression was significantly associated with the overall survival of these patients (p=0.007 and p=0.040, respectively). For in vitro studies, the magnetic-activated cell sorting (MACS) system was used to isolate CD24+ and CD24- cell populations from RMCCA1 cells. CD24+ RMCCA1 cells had increased chemoresistance, adhesion (p=0.004), motility (p<0.001), migration (p<0.001) and invasion (p<0.001) capabilities when compared to CD24- cells. The matrix metalloproteinase (MMP)-7 was significantly elevated in CD24+ RMCCA1 cells (p=0.01). We found that inhibition of CD24 using siRNA silencing significantly decreased the invasive capacity of RMCCA1 cells. Both clinical and in vitro studies suggest that expression of CD24 is associated with cholangiocarcinoma disease progression. CD24 may thus serve as a new target for directed molecular therapy of cholangiocarcinoma.

Correlation of HBV and HCV with CH, LC, HCC in liver biopsied tissue at Rajavithi Hospital.

Retrospective study in Clinicopathology of 66 surgical liver tissue from adult Thai patients admitted at Rajavithi Hospital, in Bangkok, during December 2002-September 2003 (10 month periods). The main purposes are: 1) To find the correlation of HBV, HCV with CH, LC, HCC. 2) To compare the correlation of Hepatocyte, AFP, CEA (IHC) in malignant cells, which one is the best usage to confirm the diagnosis of HCC in both primary and metastasis. 3) To review the clinicopathology of all these 66 liver samples. The results were significant correlation of HBsAg (serology) with HCC (p = 0.010), and also significant correlation of HBsAg (IHC in liver tissue) with CH, LC (p = 0.038, 0.021 respectively). Although no significant correlation (p > 0.05) of HCV (positive anti HCV) with CH, LC, HCC; the causes due to the small sample sizes and short period study are possibly bias factors. The authors concluded that Hepatocyte or Hep-Par I is the best immunocellular marker for malignant liver cells both in primary and metastasis (p < 0.001). The AFP, CEA show no correlation (p = 0.999, 0.670). The authors found other interesting non-viral related liver disease, common, uncommon, tumor and tumor-like (pseudotumor) lesions in the liver from the present study. The results of significant correlation of HBV (HBsAg) with CH, LC, HCC is one good evidence to further support The National HBV Vaccine Program for the uninfected population, which has been sponsored by the Thai Government, The Ministry of Public Health since 1992 and be one of the best and successful Thai Public-Health Policy.

A two-phase study model for the standardization of HER2 immunohistochemical assay on invasive ductal carcinoma of the breast.

OBJECTIVES: To develop and verify a standardized protocol for HER2 immunohistochemical assays on invasive ductal carcinoma of the breast in Thailand. MATERIAL AND METHOD: A two-phase study approach was employed. In the Phase One, after verifying the proposed protocol that adopted the HercepTest procedure using readily available primary antibodies, CB11 and A0485, Lab 1 performed the HER2 immunohistochemical staining for 137 cases of invasive ductal carcinoma twice with two types of the antibody. Nine pathologists from 8 centers independently examined and scored all the 2 x 137 stained slides that were blinded for antibody type. Interobserver reliability was calculated using pair-wise kappa. Following discussion of the results, the Phase Two study was planned. Lab 2 and Lab 3 independently performed the HER2 staining according to the protocol for 60 invasive breast carcinoma cases. The same group of pathologists scored 2 x 60 stained slides that were masked for laboratories. Interobserver reliability and interlaboratory agreement from each pathologist were calculated using kappa statistics. Three interpreted categories--namely negative, equivocal and positive tests were used in the analyses. RESULTS: Phase One study showed interobserver agreement between pairs varied from kappa 0.75 (95%CI, 0.68-0.82) to 0.06 (95%CI, 0-0.14) while Phase Two study obtained pair-wise kappa scores ranged from 0.84 (95%CI, 0. 80-0.89) to 0. 65 (95%CI, 0.59-0.71). Interlaboratory kappa for each pathologist was 0.67 (95%CI, 0.61-0.73). CONCLUSION: The standardization of HER2 immunohistochemical assay was achieved through this two-phase study model. It had added benefits of improving pathologists' expertise and verifying the HER2 testing protocol to be used in Thailand.

Leiomyosarcoma in peripheral nerve: the first case report.

A neoplasm of the peripheral nerves can be obscured, especially during the early phase. The authors report a patient with sciatic nerve leiomyosarcoma. The patient's presentation and initial management are unique. A 51-year-old man with clinical manifestations of von Recklinghausen's disease reported numbness and weakness of the left leg for one and a half years. The symptoms gradually progressed. The symptoms were consistent with peripheral neuritis. The patient developed foot drop one month before coming to our service. Two episodes of biopsy confirmed leiomyosarcoma. A long, large sciatic nerve leiomyosarcoma was found intra-operatively, positioned from the upper thigh to the point where the tibial nerve passes beneath the upper margin of the soleus muscle. Surgical resection was done and confirmed the diagnosis. Decreased sensation was still intact after resection.