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Objectives ROS1 rearrangement has been found in a subset of lung cancer and ROS1- rearranged tumors are sensitive to ALK kinase inhibitors. This study sought to evaluate the clinicopathological implications and histomorphological characteristics of ROS1 -rearranged tumors, especially micropapillary and aerogenous spread growth and to investigate the usefulness of ROS1 immunohistochemistry as a diagnostic test for ROS1 rearrangement. Materials and methods ROS1 rearrangement characterizations by fluorescence in situ hybridization and ROS1 protein and E-cadherin expression by immunohistochemistry were performed using 754 non-small cell lung cancer surgical specimens. Results ROS1 rearrangement was identified in 10 samples. Histologically, all 10 ROS1 -rearranged tumors harbored an adenocarcinoma component. Significantly, we noted a high association between ROS1 rearrangement with a micropapillary component ( p < 0.001), aerogenous spread ( p = 0.002), and E-cadherin loss ( p = 0.049). Survival analysis showed that ROS1 rearrangement was significantly associated with a higher risk of tumor recurrence ( p = 0.024). The best criterion to detect ROS1 -rearrangement by immunohistochemistry was an H-score of ≥100, with a sensitivity and specificity of 90% and 93.5%, respectively. Conclusions ROS1 -rearranged adenocarcinoma exhibited distinct morphological and clinicopathological features. Decreased membranous E-cadherin expression and aerogenous spread may be associated with worse disease-free survival. ROS1 immunohistochemistry correlated well with ROS1 gene rearrangement. [ABSTRACT FROM AUTHOR]

Aims: The anaplastic lymphoma kinase gene ( ALK) has attracted considerable attention as a potential molecular target in non-small-cell lung cancer (NSCLC). However, it is unclear whether ALK alterations are acquired during the metastatic progression of NSCLC. Methods and results: ALK status and ALK expression were evaluated in a series of 67 primary NSCLCs and their corresponding metastatic lesions using fluorescence in-situ hybridization and immunohistochemistry. ALK rearrangement was detected in 7.5% (5/67) of the primary tumours and in 9.0% (6/67) of the metastases ( P < 0.001). ALK copy number gain (CNG) was detected in 1.5% (1/67) of the primary tumours and in 35.8% (24/67) of the metastases. Whereas ALK rearrangement was detected only in adenocarcinomas, CNG was identified in various histological subtypes of NSCLC. ALK expression was detected in 11.9% (8/67) of the primary tumours and in 25.4% (17/67) of the metastatic lesions. Conclusions: ALK alteration and ALK expression can be acquired during metastatic progression in NSCLC, and ALK CNG is associated with ALK expression. [ABSTRACT FROM AUTHOR]

• Eosinophil and M2 macrophage infiltration were directly associated distant metastasis and tumor budding. • TILs were inversely associated with distant metastasis and tumor budding. • Eosinophil and CD163+ macrophages, and TILs infiltration were independent predictor for DMFS. Malignant tumors are complex structures that must interact with the surrounding environment for growth and invasiveness. This study aimed to comprehensively catalogue the features of immune cell stromal infiltrates within tumor tissue and peri-tumoral tissue and to determine whether these features have prognostic value in cervical squamous cell carcinoma (CxSCC). Immune stromal features in primary tumors in 122 patients enriched for CxSCC were histologically and immunohistochemically characterized. Distant metastasis was positively correlated with tumor-node-metastasis (TNM) stage (P < 0.001), lymph-vascular invasion (LVI) (P < 0.001), lymph node metastasis (LNM) (P < 0.001), and tumor budding (P = 0.012). Distant metastasis was also associated with the eosinophil infiltration (P = 0.006); Stromal, intratumoral, invasive-margin, squamous intraepithelial lesion (SIL), and perivascular tumor-infiltrating lymphocytes (TILs); CD68+, CD163+, and CD204+ macrophage infiltration. Multivariate proportional hazard regression analyses revealed that LVI; TNM stage; lymph node metastasis; tumor budding; eosinophil infiltration; CD163+ macrophage infiltration; and stromal and intratumoral TILs were independent predictors of poor DMFS in patients with CxSCC. Primary tumor immune stromal features can be useful in predicting distant metastasis in CxSCC. [ABSTRACT FROM AUTHOR]

Objectives: Activating mutations in the epidermal growth factor receptor (EGFR) kinase domain are correlated with dramatic clinical responses in non-small cell lung cancer patients treated with EGFR-tyrosine kinase inhibitors (TKIs). The two most common EGFR mutations, representing 85–90% of EGFR mutations, are the E746_A750 deletion in exon 19 and the L858R point mutation in exon 21. We conducted this study to evaluate the suitability of mutation-specific antibodies that can detect E746_A750 deletion and L858R mutant EGFR proteins by immunohistochemistry (IHC). Materials and methods: In a cohort of consecutive patients with surgically resected lung adenocarcinomas (n =240), mutant EGFR protein expression was assessed by IHC using specific antibodies (clone SP111 and SP125) to the 2 major forms of EGFR mutations. Immunoreactivity was scored as 0–3, and the results were compared with the EGFR-mutational status. Results: With a cutoff value of IHC 2+ for SP 111 (anti-EGFR E746_A750 del antibody) and SP 125 (anti-EGFR L858R antibody), both antibodies showed high specificity (99.0% and 89.7%, respectively) and sensitivity (70.6% and 80.4%, respectively). While cases with IHC scores of 3 using these 2 antibodies positively correlated with the EGFR-mutational status, cases with IHC scores lower than 3+ showed variable results regarding EGFR-mutational status. Conclusion: Although each antibody showed relatively high specificity, some EGFR-mutant cases were not detected by the mutation-specific antibodies. Various forms of exon 19 deletions, except E746_A750, were rarely detected by the mutant-specific antibody. Therefore, IHC-negative cases require further molecular analysis to confirm the presence of EGFR mutations. [ABSTRACT FROM AUTHOR]