Hideki Marushima

Survival significance of coexisting chronic obstructive pulmonary disease in patients with early lung cancer after curative surgery

The impact of chronic obstructive pulmonary disease (COPD) severity on survival after curative resection of early‐stage lung cancer (NSCLC) has not been sufficiently elucidated.

Epidermal growth factor receptor mutations in adenocarcinoma in situ and minimally invasive adenocarcinoma detected using mutation-specific monoclonal antibodies.

OBJECTIVES Epidermal growth factor receptor (EGFR) mutation rates in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) were studied using both DNA analysis and mutation-specific immunohistochemistry. MATERIALS AND METHODS The peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method was used to detect mutations in exons 18, 19, 20, and 21 of the EGFR gene in DNA samples extracted from paraffin-embedded tissue sections. Simultaneously, immunohistochemical analysis with two EGFR mutation-specific monoclonal antibodies was used to identify proteins resulting from an in-frame deletion in exon 19 (E746_A750del) and a point mutation replacing leucine with arginine at codon 858 of exon 21 (L858R). RESULTS Forty-three tumors (22 AIS and 21 MIA) were examined. The EGFR mutation rate in AIS detected by DNA analysis was 27.3% (L858R, 5/22; exon 19 deletion,1/22), whereas that detected in MIA was 42.9% (L858R,4/21; exon 19 deletion,5/21). Mutations detected by immunohistochemical analysis included 22.7% (L858R, 4/22; exon 19 deletion, 1/22) in AIS and 42.9% (L858R, 4/21; exon 19 deletion, 5/21) in MIA. Although some results were contradictory, concordant results were obtained using both assays in 38 of 43 cases (88.4%). CONCLUSION DNA and immunohistochemical analyses revealed similar EGFR mutation rates in both MIA and AIS, suggesting that mutation-specific monoclonal antibodies are useful to confirm DNA assay results.

Accuracy of the cobas EGFR Mutation Assay in Non–small-cell Lung Cancer Compared With Three Laboratory-developed Tests

Micro‐Abstract Rapid and precise mutation assays are essential to select patients with lung cancer who may respond to treatment with epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors. Using the same specimens, the reliability of the cobas EGFR assay was compared with 3 commonly used laboratory‐developed tests. High concordance rates and &kgr;‐coefficients were obtained between the cobas EGFR assay and the laboratory‐developed tests. Background: The reliability of the cobas EGFR assay to detect epidermal growth factor receptor (EGFR) mutations in non–small‐cell lung cancer (NSCLC) as an in vitro diagnostic test was compared with 3 laboratory‐developed tests (LDTs). Materials and Methods: After screening for EGFR mutations using formalin‐fixed‐paraffin‐embedded NSCLC tissue sections using the cobas EGFR assay, 151 samples were further tested with 3 LDTs; the peptide nucleic acid‐locked nucleic acid polymerase chain reaction (PCR) clamp, PCR invader, and Cycleave assays. The cobas EGFR assay performance was evaluated by determining the concordance rate and &kgr;‐coefficient between the assays. In samples exhibiting discrepancies in the EGFR mutation status in the 4 assays, next‐generation sequencing was performed to confirm mutated sequences. Results: Concordance rates and &kgr;‐coefficients between the cobas EGFR assay and the other tests were 96.0% and 0.921 for the peptide nucleic acid‐locked nucleic acid PCR clamp assay, 94.0% and 0.881 for the PCR invader assay, and 96.7% and 0.934 for the Cycleave assay, respectively. Data showed very good agreement with the other assays. Precise mutated sequences or exons in the EGFR gene matched in 137 samples (90.7%). Different results were obtained in 4 samples (2.6%), owing to systemic limitations of the assay. Next‐generation sequencing of 10 (6.6%) samples with discordant results exhibited a concordance rate of 60% to 80% in each assay. Conclusions: The cobas EGFR assay showed high concordance rates and &kgr;‐coefficients between the 3 compared LDTs and can be used to select patients who would benefit from EGFR‐tyrosine kinase inhibitors.

Difference in Postsurgical Prognostic Factors between Lung Adenocarcinoma and Squamous Cell Carcinoma

PURPOSE The aim of this study was to compare the clinicopathologic prognostic factors between patients who underwent lung resection for adenocarcinoma (AD) and those with squamous cell carcinoma (SQ). METHODS A database of patients with lung AD or SQ who underwent surgery with curative intent in our department from January 2008 to December 2014 was reviewed. Associations between various clinicopathologic factors, postsurgical recurrence-free survival (RFS), and overall survival (OS) were analyzed to find significant prognostic factors. RESULTS A total of 537 lung cancer patients (AD, 434; SQ, 103) were included in this study. Although RFS was similar in patients with AD and SQ, OS was significantly poorer in those with SQ. Multivariate analysis in patients with AD revealed that age (≥69 vs. <69), lymphatic invasion, and histologic pleural invasion (p0 vs. p1-3) were associated with RFS, while gender and pleural invasion were associated with OS. In SQ, however, smoking, clinical stage, and pulmonary metastasis were associated with RFS in the multivariate analysis. CONCLUSION Since significant postoperative prognostic factors are quite different between lung AD and SQ, these two histologic types should be differently analyzed in a clinical study.

Successful Resection of a Mediastinal Nonseminomatous Germ CellTumor Whos Response to Induction Chemotherapy was Evaluated byFluorodeoxyglucose-Positron Emission Tomography

Mediastinal germ cell tumors are rare malignant tumors whose current management strategy involves making a prompt diagnosis and providing an appropriate chemotherapy. However, there is as yet no consensus regarding the optimal management postchemotherapy. We encountered the case of a 23-year-old man who was diagnosed as having a mediastinal nonseminomatous germ cell tumor. We evaluated its response to induction chemotherapy by fluorodeoxyglucose-positron emission tomography/computed tomography. We performed complete surgical excision of the residual tumor postchemotherapy. Histopathologic examination of the surgical specimen showed no viable tumor cells.

Glucose Uptake Values in Positron Emission Tomography Are Useful to Predict Survival after Sublobar Resection for Lung Cancer.

Background To assess the reliability of maximum standardized uptake values (SUVmax) at the primary lesion in 18‐fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG‐PET/CT) for identifying patients with lung cancer who were most likely to be cured by sublobar resection (SR). Methods We retrospectively reviewed the medical records of 120 patients who underwent SR for clinical (c)‐stage IA + IB lung cancer after 18FDG‐PET/CT. Various factors, including tumor size, SUVmax at the primary site, and microscopic tumor invasion, were examined to identify their association with postsurgical survival. Prognoses of patients undergoing SR were compared with those of 272 patients undergoing lobectomy and lymphadenectomy during the same period. Results The 5‐year recurrence‐free survival (RFS) and overall survival (OS) rates in all patients undergoing SR for c‐stage IA + IB disease were 79.5% and 82.2%, respectively. In multivariate analysis, a lack of microscopic pleural invasion and SUVmax ≤ 3.0 significantly correlated with better RFS and OS in patients undergoing SR. Though there were no significant differences in RFS and OS following SR and lobectomy for c‐stage IA + IB or IA disease, RFS was significantly inferior in nonintentional SR (NISR) than in lobectomy in c‐stage IA disease (p < 0.01). However, in NISR identified based on SUVmax ≤ 2.0, RFS was comparable to those in lobectomy (p = 0.5371). Conclusion When certain subgroups of patients are accurately identified based on preoperative SUVmax, SR can be a highly curative surgical method for lung cancer.

Different EGFR gene mutations in two patients with synchronous multiple lung cancers: A case report

Routine clinical and pathological evaluations to determine the relationship between different lesions are often not completely conclusive. Interestingly, detailed genetic analysis of tumor samples may provide important additional information and identify second primary lung cancers. In the present study, we report cases of two synchronous lung adenocarcinomas composed of two distinct pathological subtypes with different EGFR gene mutations: a homozygous deletion in exon 19 of the papillary adenocarcinoma subtype and a point mutation of L858R in exon 21 of the tubular adenocarcinoma. The present report highlights the clinical importance of molecular cancer biomarkers to guide management decisions in cases involving multiple lung tumors.

PD-L1 Expression in Non-Small-Cell Lung Cancer Including Various Adenocarcinoma Subtypes

Purpose: Knowledge regarding programmed death-ligand 1 (PD-L1) expression in lung cancer is limited. We aim to clarify PD-L1-positive expression in non-small-cell lung cancer (NSCLC), including adenocarcinoma subtypes. Methods: In all, 90 NSCLC specimens containing various adenocarcinoma subtypes, in addition to squamous cell carcinoma and large-cell carcinoma were selected. PD-L1 was immunohistochemically stained by murine monoclonal antibody clone 22C3. Results: When PD-L1-positive expression was defined by tumor proportion score (TPS) ≥1%, the positive cases were 0/11 in adenocarcinoma in situ, 0/12 in minimally invasive adenocarcinoma, 1/10 in lepidic predominant adenocarcinoma, 1/13 in papillary predominant adenocarcinoma, 8/14 in acinar predominant adenocarcinoma, 6/11 in solid predominant adenocarcinoma, 0/3 in micropapillary predominant adenocarcinoma, 0/4 in invasive mucinous adenocarcinoma, 4/9 in squamous cell carcinoma, and 2/3 in large-cell carcinoma. PD-L1 positivity was higher in males, smokers, advanced pathologic stages, positive vessel invasion, and positive lymphatic invasion. Postoperative survival analysis revealed that PD-L1-positive expression was a significantly worse prognostic factor in univariate analysis for recurrence-free survival (RFS). Conclusion: PD-L1-positive tumors were frequent in acinar predominant adenocarcinoma and solid predominant adenocarcinoma than other adenocarcinoma subtypes. PD-L1 expression seemed to increase according to pathologic tumor progression, suggesting a worse postoperative prognosis in NSCLC patients.

Unusual presentation of pulmonary lymphoepithelioma-like carcinoma.

Primary pulmonary lymphoepithelioma‐like carcinoma (LELC) is a rare malignant tumour with histological features similar to undifferentiated nasopharyngeal carcinoma. A close association is known to exist between pulmonary LELC and Epstein–Barr virus infection in Southeast Asian countries. We report a 69‐year‐old man with pulmonary LELC arising from a thin‐walled cavity with a smooth inner surface and characterized by an unexpectedly rapid progression.