PD-L1 expression and infiltration by CD4+ and FoxP3+ T cells are increased in Xp11 translocation renal cell carcinoma and indicate poor prognosis.

AIMS: Interaction between programmed death-1 ligand (PD-L1) and its receptor programmed death 1 (PD-1) on T cells inactivates antitumour immune responses. PD-L1 expression has been associated with poor prognosis in renal cell carcinoma (RCC) and predicts adverse outcome. This study was designed to evaluate the impact of PD-L1 expression and the immune microenvironment on the clinical outcome in Xp11 translocation renal cell carcinoma (TRCC) and, therefore, their potential relevance as prognostic biomarkers. METHODS AND RESULTS: The present retrospective analysis investigated expression of PD-L1 and immune cells CD8, CD4, CD3, forkhead box protein 3 (FoxP3) and PD-1 in TRCC compared to other types of RCC. FFPE specimens were collected between 2011 and 2017 from 311 patients who underwent nephrectomy at our institution for RCC. Specimens were immunostained for PD-L1, CD8, CD4, CD3, FoxP3 and PD-1, and an outcome analysis was conducted. PD-L1 expression rate was highest in TRCC (68%, 16 of 25), followed by mucinous tubular and spindle cell RCC and collecting duct carcinoma (33%, one of three), papillary RCC (27%, seven of 26), clear cell RCC (16%, 29 of 233), chromophobe RCC (11%, two of 18) and multilocular cystic RCC (0%, none of three). In TRCC, PD-L1 expression was associated with poor recurrence-free survival (RFS) (P = 0.041). The CD4high and FoxP3high groups showed a significantly shorter RFS (P = 0.05 and P = 0.031, respectively) compared to CD4low and FOXPlow groups. CONCLUSION: PD-L1 expression was higher in TRCC than in other types of RCC. High PD-L1 tumour cell expression and tumour infiltration by CD4+ and FoxP3+ immune cells were associated with poor RFS in TRCC.

MUC5AC and MUC5B enhance the characterization of mucinous adenocarcinomas of the lung and predict poor prognosis.

AIMS: From the viewpoint of histogenesis, lung adenocarcinoma can be subdivided into two groups: terminal respiratory unit (TRU) and non-TRU types. We recently reported a non-TRU type adenocarcinoma designated as ciliated adenocarcinoma (we now prefer central type adenocarcinoma). We suggest reasons that mucinous adenocarcinoma should encompass central type adenocarcinoma to represent its biological characteristics as non-TRU type adenocarcinoma. METHODS AND RESULTS: Mucin (MUC)5AC and MUC5B were expressed more significantly in non-TRU type adenocarcinoma (P < 0.01). Thirty-five (76.1%) and 45 cases (97.8%) of 46 non-TRU type adenocarcinoma showed positivity for MUC5AC and MUC5B. Twelve (7.6%) and eight (5.1%) cases of 157 TRU type adenocarainoma showed positivity for MUC5B and MUC5AC. NKX2-1 gene expression was measured with quantitative reverse transcription-polymerase chain reaction (qRT-PCR). ΔΔCt of NKX2-1 gene expression was 6.79 for TRU type adenocarcinoma and 0.6 for non-TRU type adenocarcinoma. Overall survival and disease-free survival were poorer in non-TRU type adenocarcinoma (P = 0.02 and P = 0.03). A multivariate test also showed that non-TRU type adenocarcinoma is an independent prognostic factor (P = 0.04). CONCLUSION: MUC5AC and MUC5B were specific makers for non-TRU adenocarcinoma, including both central type adenocarcinoma and mucinous adenocarcinoma. We suggest that non-TRU type adenocarcinoma presents a poorer prognosis, so it should be regarded separately from TRU type adenocarcinoma.

Correlation between biological marker expression and F-fluorodeoxyglucose uptake in cervical cancer measured by positron emission tomography.

BACKGROUND: This study aimed to determine whether several biologic markers were associated with (18)fluorine-fluorodeoxyglucose ((18)F-FDG) uptake in patients with carcinoma of the cervix. PATIENTS AND METHODS: 60 patients with International Federation of Gynecology and Obstetrics (FIGO) stages IA2 to IIB cervical cancer, who underwent (18)FDG positron emission tomography/computed tomography (PET/CT), were included in the current study. All patients underwent radical hysterectomy. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (GLUT1), carbonic anhydrase-IX (CA-IX), vascular endothelial growth factor (VEGF), hexokinase type I (HK-I), hexokinase type II (HK-II), and cytoplasmic and nuclear hypoxia-inducible factor (HIF) 1α. RESULTS: The expression of GLUT1 (p = 0.005), VEGF (p = 0.021), HK-II (p = 0.009), and cytoplasmic HIF1α (p = 0.024) was significantly associated with a higher median standardized uptake value (SUVmax). There was a positive correlation between (18)F-FDG uptake and GLUT1 (p = 0.008), CA-IX (p = 0.030), HK-II (p < 0.001) as well as cytoplasmic HIF1α (p = 0.016), whereas this relationship was not observed among the VEGF, HK-I and nuclear HIF1α. CONCLUSION: The data presented in this study indicate that (18)F-FDG uptake is associated with the presence of GLUT1, VEGF, nuclear HK-II, and cytoplasmic HIF1α. There was also a significant correlation among the rate of expression of GLUT1, HK-II, cytoplasmic HIF1α, and CAIX in carcinomas of the cervix.