Molecular Detection of FGFR2 Rearrangements in Resected Intrahepatic Cholangiocarcinomas: FISH Could Be An Ideal Method in Patients with Histological Small Duct Subtype.

Background and Aims: Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer for which effective therapeutic agents are lacking. Fibroblast growth factor receptor 2 (FGFR2) has become a promising therapeutic target in ICC; however, its incidence and optimum testing method have not been fully assessed. This study investigated the rearrangement of FGFR2 in intrahepatic cholangiocarcinoma using multiple molecular detection methods. Methods: The samples and clinical data of 167 patients who underwent surgical resection of intrahepatic cholangiocarcinoma in Zhongshan hospital, Fudan university were collected. The presence of FGFR2 gene rearrangement was confirmed using fluorescence in situ hybridization (FISH) and targeted next-generation sequencing (NGS). FGFR2 protein expression was determined using immunohistochemistry (IHC). The concordance between the methods was statistically compared. PD-L1 expression was also assessed in this cohort. The clinicopathological characteristics and genomic profile related to FGFR2 rearrangements were also analyzed to assist candidate-screening for targeted therapies. Results: FGFR2 rearrangement was detected in 21 of the 167 ICC cases (12.5%) using FISH. NGS analysis revealed that FGFR2 rearrangement was present in 16 of the 20 FISH-positive cases, which was consistent with the FISH results (kappa value=0.696, p<0.01). IHC showed that 80 of the 167 cases (48%) were positive for FGFR2 expression, which was discordant with both FISH and NGS results. By comparison, FGFR2-positivity tended to correlate with unique clinicopathological subgroups, featuring early clinical stage, histologically small duct subtype, and reduced mucus production (P<0.05), with improved overall survival (p<0.05). FGFR2-positivity was not associated with PD-L1 expression in ICCs. In genome research, we identified eight partner genes fused with FGFR2, among which FGFR2-BICC1 was the most common fusion type. BAP1, CDKN2A, and CDKN2B were the most common concomitant genetic alterations of FGFR2, whereas KRAS and IDH1 mutations were mutually exclusive to FGFR2 rearrangements. Conclusions: FISH achieved satisfactory concordance with NGS, has potential value for FGFR2 screening for targeted therapies. FGFR2 detection should be prioritized for unique clinical subgroups in ICC, which features a histological small duct subtype, early clinical stage, and reduced mucus production.

Relationship between PD-L1 expression and molecular aberrances in lung adenocarcinoma with solid components.

Background: Previous studies have evaluated the expression of programmed cell death ligand 1 (PD-L1) in terms of genetic mutation in lung adenocarcinoma (LUAD). However, there are no corresponding large-sample studies in Chinese patients with LUAD with solid components (LUAD-SC). Furthermore, it remains unknown whether the relationship that exists between PD-L1 expression levels and clinicopathological and molecular profiles in small biopsy specimens is consistent with that in surgically-resected specimens. The present study explored the clinicopathological features and genetic correlation of PD-L1 expression in LUAD-SC. Methods: We collected 1,186 LUAD-SC specimens from Fudan University, Zhongshan Hospital. The tumors were divided into PD-L1 negative, low, and high groups according to the tumor proportion score (TPS)-assessed expression of PD-L1. The mutational information of all specimens was assessed. Each group's clinicopathological features were also assessed. The relationship between PD-L1 expression levels and clinicopathological features, the overlap with driver genes and the prognostic value were analyzed. Results: In 1,090 resected specimens, a high PD-L1 expression level was more prevalent in the group with predominant SCs, which was remarkably correlated with lymphovascular invasion and a more advanced clinical stage. In addition, the PD-L1 expression level was significantly related to EGFR, KRAS, and BRAF mutations and ROS1 fusions. Meanwhile, in 96 biopsy specimens, the solid-dominant type and EGFR showed a significant difference in PD-L1 expression. Furthermore, compared with their resected counterparts, the biopsy specimens were significantly associated with solid predominant, advanced tumor-node-metastasis (TNM) stage, and high PD-L1 expression. Finally, high PD-L1 expression can be considered a poor prognostic factor for overall survival (OS). Conclusions: LUAD-SC with high PD-L1 expression levels is linked to unique clinicopathologic characteristics as well as driver mutations. It is important to evaluate the percentage of solid components in both punctured and excised specimens, which may help identify cases of high PD-L1 expression.

Organizing pneumonia secondary to lung cancer of unknown primary site.

BACKGROUND: Secondary organizing pneumonia (OP) is associated with other pathological conditions, such as infections, drugs, cancers and radiotherapy. Lung cancer-associated secondary OP has rarely been reported. CASE REVIEW: In this study, we reported on a case of secondary OP caused by lung cancer. The patient was initially diagnosed with community-acquired pneumonia and then cryptogenic organizing pneumonia by CT scan-guided and transbronchial lung biopsy. Poor response to anti-infection or corticosteroid therapy prompted us to search for underlying disease. A TBNA biopsy of the 4R mediastinal lymph node revealed the diagnosis of lung cancer. CONCLUSION: OP secondary to lung cancer of unknown primary site are rare. When OP patients have lymphadenopathy or poor response to glucocorticoid, a more differential diagnosis should be considered, especially for avoiding the misdiagnosis of a malignancy.