Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) plays a crucial role in tumorigenesis of lung cancer. However, the therapeutic potential for anti CEACAM6 monoclonal antibody (mAb) has only been limitedly explored. Here, we evaluate the therapeutic potential of naked anti CEACAM6 mAb against lung adenocarcinoma. Clone 8F5, recognizing B domain of CEACAM6, is established by immunizing A549 cells and screening for clones double positive for A549 and CEACAM6-Fc recombinant protein. We found that 85.7% of 70 resected lung adenocarcinoma tissue sections were positive for CEACAM6, whereas all squamous cell carcinoma examined were negative. A549 cells with high levels of CEACAM6 demonstrated more aggressive growth nature and showed increased paclitaxel chemosensitivity upon 8F5 binding. Treatment with 8F5 to A549 decreased cellular CEACAM6 expression and reversed anoikis resistance. 8F5 also decreased cellular status of Akt phosphorylation and increased apoptosis via caspase activation. In a mouse model of lung adenocarcinoma with xenotransplanted A549 cells, 8F5 treatment alone demonstrated 40% tumor growth inhibition. When combined with paclitaxel treatment, 8F5 markedly enhanced tumor growth inhibition, up to 80%. In summary, we demonstrate that anti CEACAM6 mAb is an effective therapeutic treatment for lung adenocarcinoma whose effect is further enhanced by combined treatment with paclitaxel.

Son SM, et al. J Gastric Cancer. 2024 Dec;25:e2. https://doi.org/10.5230/jgc.2025.25.e2

Background: Malignant pleural effusion (MPE) is a common complication of cancer cell metastasis to the pleura. Discrimination between MPE and benign pleural effusion is necessary to design treatment strategies. Cytology is important for the diagnosis of MPE. Carcinoembryonic antigen (CEA) is an epithelial biomarker with a strong staining pattern in adenocarcinomas. Here, the diagnostic performances of liquid-based cytology (LBC), cell block (CB) preparation, and CEA immunostaining for the detection of malignancy in effusion cytology were compared in a large case series. Methods: In a single institution, 1,014 cytology samples from 862 patients were retrospectively collected and reviewed between January 2013 and November 2015. Ethanol-fixed, paraffin embedded CB of pleural effusions was analyzed by CEA immunostaining. Diagnostic values were compared among LBC, CB, CEA immunostaining, and the combination of two methods. Results: The sensitivity and specificity of the CB preparation were 94.3% and 98.7%, respectively, compared with 81.3% and 99.4% for LBC preparations, respectively. Combination of LBC and CB increased sensitivity by 98.3%. Although the accuracy of CEA staining itself was moderate (sensitivity, 89.8%), the combined use of CB and CEA tumor marker increased the detection rate of malignancy (sensitivity, 100%; specificity, 100%), compared with that of cytology (LBC or CB) alone. Conclusions: The sensitivity and specificity for the diagnosis of MPE could be improved by integrating the CB and CEA staining into LBC in routine clinical practice to improve diagnostic accuracy.

Kim H, et al. J Gastric Cancer. 2025 Oct;25:e46. https://doi.org/10.5230/jgc.2025.25.e46

PurposeHistologic change is a resistant mechanism in lung cancer. The most common histological change is the switch from adenocarcinoma (AdenoCa) to small cell carcinoma (SCC) against to tyrosine kinase inhibitors (TKI). However, it is not clear whether other treatment modalities are involved in the histologic changes.Materials and MethodsWe investigated histological changes in eight cases, after various treatments, and compared the molecular profiles between primary tumors and changed tumors using exome sequencing where tissue was available.ResultsThree cases of AdenoCa that were changed into SCC retained the initial mutations after TKI and/or surgical treatment. After treatment with TKI and immunotherapy, an EGFR (epidermal growth factor receptor)-mutant AdenoCa changed to squamous cell carcinoma (SqCa). SqCa in a patient treated with surgery was changed into combined AdenoCa and SqCa. These two cases showed the same genetic variations between the two distinct non–small cell carcinomas (NSCC). Three patients experienced two histologic changes, which the changed tumors returned to its original subtype or changed to a combined tumor after treatments. Four cases showed combined histology in the first or second change.ConclusionThe histology of NSCC can be changed to a single pattern or combined subtypes after various treatment modalities, and the phenotypic changes seem not fixed. Therefore, additional morphologic changes may occur regardless of their genetic status and types of treatments. To refine the new treatment strategy, consecutive repeated biopsies in progressive disease or recurrent tumor are necessary.

Primary retroperitoneal mucinous cystic neoplasms are rare retroperitoneal tumors, which are histologically similar to mucinous cystic neoplasms of the ovaries. Only 31 cases of primary retroperitoneal mucinous cystic neoplasm with borderline malignancy (PRMCN-BM) have been reported (26 in women and five in men). We describe an additional male patient with PRMCN-BM. A 39-year-old man presented to our hospital with back pain. Twelve years earlier, he had undergone an orchiectomy for a germ cell tumor. Computed tomography showed a 6.9- × 4.4-cm cystic mass in the left pararenal space. Laparoscopic mass excision was performed, and a unilocular cystic mass was found in the pararenal space near the lower pole of the left kidney. A histopathological examination showed a cyst lined by atypical mucinous intestinal epithelium without stromal invasion. Targeted next-generation sequencing identified two hotspot mutations, with one each in the KRAS and GNAS genes. Outpatient follow-up 10 months after surgery showed no evidence of tumor recurrence. PRMCNs are extremely rare retroperitoneal neoplasms, especially in men. These neoplasms are rarely considered in the differential diagnosis of retroperitoneal masses, and their preoperative diagnosis is difficult. Evaluation of additional patients is required to better determine the prognosis of PRMCNs and the optimal postoperative follow-up.