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Background: GC33 is a recently developed monoclonal antibody against human glypican-3 (GPC3), which is significantly upregulated in hepatocellular carcinoma (HCC). GC33 recognizes a GPC3 ectodomain and shows significant antitumour activity in vivo. Thus, humanized GC33 antibody may be a promising tool for treating HCC having cell surface GPC3 expression., Aims: This study aims to determine the specificity, subcellular localization and prognostic impact of GPC3 immunoreactivity detected by GC33 in HCC clinical specimens., Methods: Immunohistochemical analysis was performed for 194 cases of resected HCC and prognostic analysis was performed for 185 eligible cases. Two antigen retrieval methods (autoclave and protease pretreatments) were used for immunohistochemistry and compared. The immunoscore system reflecting circumferential membranous GPC3 immunoreactivity was developed using either the autoclave or protease methods. The GPC3 mRNA level was analysed by quantitative real-time reverse transcription-polymerase chain reaction., Results: GC33 immunostaining after autoclave is a sensitive method and revealed the GPC3 expression (≥20% of tumour cells) in the majority (77%) of HCC samples tested. Alternatively, protease pretreatment showed lower sensitivity, but was superior for evaluating the intensity and subcellular localization of GPC3. Correlation between immunoscores and the GPC3 mRNA level was also confirmed. Subsequent clinicopathological analysis revealed worse prognoses in HCC patients with circumferential membranous GPC3 immunoreactivity. For HCC patients with hepatitis C virus (HCV) infection in particular, the high membranous GPC3 immunoreactivity was an independent prognostic factor for disease-free survival., Conclusions: Circumferential membranous GPC3 immunoreactivity in HCC indicates poorer prognosis particularly in patients with HCV infection., (© 2010 John Wiley & Sons A/S.)

Complete response of non–small cell lung cancer (NSCLC) with immune checkpoint inhibitor (ICI) monotherapy is rare. Here, we encountered an elderly patient who showed complete response of NSCLC following treatment with pembrolizumab. An 84‐year‐old man with a history of bloody sputum for several weeks visited a general physician. At that time, a chest X‐ray revealed a tumor shadow in the left middle lung field, and the patient was referred to our hospital. Following transbronchial biopsy, he was diagnosed with squamous cell carcinoma of the lung. Expression of programmed death ligand 1 (PD‐L1) in tumor cells was 80% or more by immunostaining. Based on the above, immunotherapy with pembrolizumab was performed as first‐line therapy. The cancer cells completely disappeared at the end of the fifth cycle. There were no side effects during the therapeutic course. Treatment with pembrolizumab continued for two years and was then discontinued at the patient's request. Since then, no tumor recurrence has been detected for about one and a half years without treatment. There have been few reports of lung cancer disappearing after treatment with pembrolizumab. In conclusion, in elderly NSCLC patients with PD‐L1 expression of 50% or more, pembrolizumab should be considered as first‐line treatment with the treatment period, and mechanism suggested in this report. [ABSTRACT FROM AUTHOR]

Aims: Stratified mucin‐producing intra‐epithelial lesion (SMILE) and invasive stratified mucin‐producing carcinoma (ISMC) are recently described cervical and penile lesions. We report an unusual case of mixed variant of penile squamous cell carcinomas with warty, usual and mucoepidermoid SMILE/ISMC features. Methods and results: A 62‐year‐old Japanese man had a glans penis lesion of one‐and‐a‐half years’ duration, suggesting malignancy. Partial penectomy and left inguinal lymphadenectomy were performed. Pathological evaluation revealed a mixed squamous cell carcinoma with warty, mucinous and usual features. The mucinous component resembled mucoepidermoid carcinoma (MEC) and SMILE/ISMC. Glandular differentiation was absent. All the diverse tumour components were negative for p16, which was confirmed by negative human papillomavirus (HPV) genotyping. The mucinous component was diffusely positive for cytokeratin 7 and largely negative for cytokeratin 5 and p63. Fluorescence in‐situ hybridisation did not detect rearrangement in the MAML2 or EWSR1 genes. The tumour was pathological stage pT2, pN1 (AJCC prognostic stage group IIIA) and was disease‐free 26 months after surgery. Conclusions: The lack of glands in the mucinous areas suggested that MEC should be separated from adenosquamous carcinoma (ASC). Penile SMILE/ISMC may occur without dependence upon HPV status. Further studies will be necessary to determine the pathogenesis and definition of penile SMILE/ISMC, the presence of true MEC arising from the glans penis and the clinicopathological differences of penile ASC, MEC and SMILE/ISMC. Herein, we refer to the SMILE‐like penile lesion as ‘mucinous penile intra‐epithelial neoplasia’. [ABSTRACT FROM AUTHOR]

Primary sarcoma is uncommon in the lung, and primary angiosarcoma is exceedingly rare. We report a case of primary pulmonary angiosarcoma of the left lung with emphasis on its growth pattern in the lung. A 48-year-old Japanese man was admitted to our hospital because of dyspnea on exertion. He was subsequently found to have left pleural effusion. Computed tomography shows a nodular lesion measuring 7 × 4 cm in his left lung. Obstruction of the left inferior lobar bronchus was observed, and endobronchial biopsy suggested angiosarcoma. Left pneumonectomy was performed. On macroscopic examination of the cut surface, multiple nodular lesions were observed particularly in portions around branches of pulmonary artery along bronchioles. Histological examination revealed vascular channel-like structure with vague lumen formations by atypical polygonal or spindle-shaped neoplastic cells. Immunohistochemically, the neoplastic cells are positive for FLI-1, ERG, CD31 and von Willebrand factor/factor VIII-related antigen, but not CD34. Angiosarcoma is a particularly rare form of primary pulmonary tumors, and this case report describes its unique macroscopic growth pattern in the lung. [ABSTRACT FROM AUTHOR]