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Abstract ROS1 rearrangements are found in 1–2% of patients with non‐small‐cell lung cancer. The detection of the rearrangements is crucial since clinically effective molecular targeted drugs are available for them. We present a case of lung adenocarcinoma with a previously unknown ROS1‐CD74 fusion variant, CD74 exon 3 fused to ROS1 exon 34, which was not detected by a conventional RT‐PCR‐based test for ROS1 fusion gene detection but identified by hybrid capture‐based next‐generation sequencing. This tumor responded to crizotinib initially and to entrectinib after relapse with brain metastasis, indicating the oncogenic activity of this novel fusion variant.

Abstract Background Dermatomyositis is associated with malignant tumors including breast cancer, and inflammatory breast cancer is considered to have a poorer prognosis than most breast cancers. Case presentation A 74-year-old Asian woman, developed erythema on her face, back, and the back of her hands, 3 weeks before attending our department. At the same time, she had noticed a right breast mass and redness of the skin of the breast. The clinical findings and vacuum aspiration biopsy diagnosed inflammatory breast cancer and neoadjuvant chemotherapy was performed. The mass and enlarged axillary lymph nodes had shrunk, therefore a total mastectomy was performed. The sentinel lymph node biopsy was negative. She was discharged 7 days after surgery without any complications. She has received a postoperative aromatase inhibitor and is alive without recurrence. The dermatomyositis also began to improve with the start of her chemotherapy and has not recurred since the surgery. Conclusions Neoadjuvant chemotherapy was performed for inflammatory breast cancer with dermatomyositis, and tumor shrinkage was confirmed. A total mastectomy without axillary lymph node dissection was performed. Dermatomyositis and breast cancer have not recurred. Dermatomyositis may have been a paraneoplastic syndrome due to breast cancer.

In epithelial tissues, intercellular adhesion structures are formed between adjacent cells via intercellular adhesion factors, such as zonula occludens (ZO-1), to maintain the structure and function of tissues and organs, thereby contributing to homeostasis. Epithelial cells are polarized into apical and basal regions by tight junctions (TJs), a type of intercellular adhesion structure, and thus, their intracellular organelles are asymmetrically distributed. Normal epithelial cells maintain their cellular function by controlling cytoskeletal reorganization, motility, and division by maintaining asymmetry in their intracellular organelles. Among the features common to many cancer tissues are abnormalities in cell polarity and intercellular adhesion. Lung adenocarcinoma consists of a mixture of five different histologic types that can be distinguished in the same section: lepidic, papillary, acinar, micropapillary, and solid patterns. Therefore, it is often difficult to accurately assess histological images because the staining differs according to the histological types. In the present study, we evaluated ZO-1 staining based on histological features observed in a single section and examined its relationship to clinicopathological features. In non-tumor areas, ZO-1 was expressed on the plasma membrane and in the cytoplasm of normal alveolar epithelial cells. However, in tumor areas, ZO-1 staining was mainly localized in the cytoplasm and on the plasma membrane only in a few cells. ZO-1-negative cases tended to have poorer prognoses in all histological types, with a poorer prognosis in the solid pattern. These results suggest that ZO-1 expression in solid-pattern lung adenocarcinoma may be a useful prognostic marker. [ABSTRACT FROM AUTHOR]

Epithelial cells form epithelial tissue structures by joining together via intercellular adhesion structures composed of intercellular adhesion factors such as zona occludins-1 (ZO-1). Epithelial cells are polarized at the apical and basal regions, and are bordered by intercellular adhesion structures called tight junctions; the organelles within epithelial cells are distributed asymmetrically. Maintenance of this asymmetry in normal epithelial cells is essential for normal cytoskeletal remodeling, movement, and cell division. The key factor regulating cell polarity is called partitioning-defective protein 3 (Par3). Abnormalities in cell polarity and intercellular adhesion are common features of many cancer tissues. Mutation and loss of cell polarity regulators contributes to the immortalization of normal cells and to the malignant transformation of cancer cells. In this study, we investigated the relationship between the subcellular localization of Par3 and ZO-1 and clinicopathological features of lung squamous cell carcinoma (lung SqCC). Both molecules were localized to the cell membrane in normal lung tissue, but the levels were lower at this location in pulmonary tumor tissue compared with normal lung tissue. Both Par3 and ZO-1 accumulated in clusters on the cell membrane (hereinafter, "foci"). Tumor size, recurrence rate, and mortality rate were significantly higher in patients with Par3 foci compared to those without Par3 foci. Rates of lymph node metastasis, recurrence, and mortality were significantly higher in patients with ZO-1 foci than in those without ZO-1 foci. The expression of Par3 and ZO-1 mRNA was not s ignificantly different in s amples from p atients with foci versus those without. These results strongly suggest that the presence of Par3 and ZO-1 foci on the membrane may be a useful prognostic marker for lung SqCC. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Cachexia has been shown to be related to mortality in patients with advanced cancers and chronic obstructive pulmonary disease. Smokers receiving surgery for lung cancer are thought to be at risk of developing cachexia postoperatively. We aimed to investigate whether 2 surrogate variables for cachexia, body mass index (BMI) and C-reactive protein (CRP) level, are predictive of mortality in smokers after complete resection of non-small-cell lung cancer. METHODS: We retrospectively examined 678 patients who underwent curative lobar resection for non-small-cell lung cancer at our hospital. Associations between clinicopathological factors and overall survival were assessed in smokers (N= 421) and never smokers (N= 257). RESULTS: Multivariate analysis of the smokers group showed that preoperative BMI <20.6 kg/m2 and CRP⩾0.13 ng/ml were risk factors for poorer prognosis, independent of age and pathological stage. In never smokers, BMI and CRP were not significantly associated with survival. Smokers in the high-risk group, defined based on preoperative BMI and CRP, had shorter survival after recurrence, although they did not have an elevated recurrence rate. Despite the absence of recurrence, they died more frequently of pneumonia or other cancers. These observations are consistent with the idea that the poor postoperative prognosis could have resulted from the progression of cachexia.CONCLUSIONS: In smokers with non-small-cell lung cancer, preoperative low BMI and elevated CRP are predictive factors for poor prognosis after complete resection, probably as a result of cachexia progression. The effective treatment of cachexia might improve postoperative prognosis. [ABSTRACT FROM AUTHOR]

Pathological stage is the most important prognostic factor in patients with lung cancer, and is defined according to the tumor node metastasis classification system. The present study aimed to investigate the clinicopathological significance of lymphatic invasion in 103 patients who underwent surgical resection of lung squamous cell carcinoma (SqCC). The patients were divided into two groups, according to the degree of lymphatic invasion: Those with no or mild lymphatic invasion (ly0-1) and those with moderate or severe lymphatic invasion (ly2-3). Ly2-3 was associated with tumor size (P=0.028), lymph node metastasis (P<0.001), venous invasion (P=0.001) and histological differentiation (P=0.047). Statistical analysis using the Kaplan-Meier method and the log-rank test indicated that overall survival was significantly reduced in patients with ly2-3 compared with those with ly0-1 (P<0.001). Multivariate analysis identified ly2-3 as an independent predictor of mortality (hazard ratio, 2.580; 95% confidence interval, 1.376-4.839). In conclusion, moderate or severe lymphatic invasion (ly2-3) indicated a high malignant potential and may be considered an independent predictor of poor prognosis in patients with SqCC of the lung. [ABSTRACT FROM AUTHOR]

Ki-67 is a nuclear protein that is expressed during the G1, S, G2 and M phases of the mitotic cell cycle. A previous study categorized tumor infiltration patterns (INF), of which INFc indicated cancer nests exhibiting infiltrative growth and an unclear boundary between tumor tissue and surrounding healthy t issue. T he present study used t he K i-67 labeling index (Ki-67 LI) as an indicator of cell proliferation, in order to examine the factors affecting INF in lung squamous cell carcinoma (SqCC). SqCC specimens (89) were classified into two groups: High-grade cell proliferation (Ki-67 LI ≥30%) and low-grade cell proliferation (Ki-67 LI <30%). However, a high Ki-67 LI was significantly associated with cases that had an INFc component [INFc(+); P=0.03]. Univariate analyses indicated that INFc(+) was a predictor of venous invasion [P=0.032; odds ratio (OR), 2.615; 95% confidence interval (95% CI), 1.085-6.305], scirrhous stromal type (P<0.001; OR, 6.462; 95% CI, 2.483-16.817) and high Ki-67 LI (P=0.018; OR, 12.543; 95% CI, 1.531-102.777). Multivariate logistic analyses indicated that high Ki-67 LI was the strongest predictor of INFc(+) (P=0.028; OR, 8.027; 95% CI, 1.248-51.624). In conclusion, high-grade cell proliferation activity may contribute to aggressive infiltrative growth of lung SqCC. [ABSTRACT FROM AUTHOR]