No Impact of PolySia-NCAM Expression on Treatment Response in Neuroendocrine Neoplasms of the Lung

Simple Summary Polysialic acids (polySia) are localized on the neuronal cell adhesion molecule (NCAM). They are expressed on numerous tumors of neural crest origin. These include lung neuroendocrine tumors such as atypical carcinoid, large cell neuroendocrine and small cell carcinomas. Interfering with polySia is considered a potential approach in the development of tumor therapies. In this study, we investigated whether polySia expression has an impact on disease progression, treatment response, and prognosis. To this end, tissue samples from 28 patients were analyzed by immunohistochemistry for polySia-NCAM presence. In conclusion, NCAM-polySia is not very useful as a prognostic factor for poor disease outcome. However, it is still interesting as a therarpeutic target for individual tumor therapy, as a majority of patients (78.6%) showed a strong staining signal for NCAM-polySia. Background: Polysialic acids (abbr. polySia) are found on numerous tumors, including neuroendocrine lung tumors. They have previously been shown to impact metastatic potential, as they can influence the signaling and adhesion properties of neuronal cell adhesion molecules (abbr. NCAM) and other cell adhesion molecules. Therefore, the aim of this small pilot study was to analyze whether there was a correlation between polySia-NCAM expression and specific clinical or histopathologic characteristics, and if polySia-NCAM expression had an impact on treatment response, disease progression and prognosis of lung neuroendocrine neoplasms. Methods: This work was based on an analysis of 28 digitized patient records and corresponding patient samples. The response to therapy was radiologically determined at the time of diagnosis and at certain intervals during therapy following the current RECIST1.1 and volumetric sphere calculation. To analyze whether polySia-NCAM expression had prognostic relevance, polySia-NCAM-positive and -negative cases were compared in a Kaplan-Meier survival analysis. Findings: A majority of 78.6% lung neuroendocrine neoplasms showed a strong staining signal for polySia-NCAM. There was a significant correlation between expression and histopathological grade (p = 0.0140), since carcinoids were less likely polySia-NCAM-positive compared to small cell lung carcinoma (abbr. SCLC) and large cell neuroendocrine carcinomas of the lung (abbr. LCNEC). There was no significant association between polySia-NCAM expression and clinical characteristics (age: p = 0.3405; gender: p = 0.6730; smoking history: p = 0.1145; ECOG: p = 0.1756, UICC8 stage: p = 0.1182) or radiologically determined disease progression, regardless of the criteria used to categorize response (RECIST 1.1: p = 0.0759; sphere: p = 0.0580). Furthermore, polySia-NCAM expression did not affect progression-free survival (p = 0.4198) or overall survival (p = 0.6918). Interpretation: PolySia-NCAM expression was more common in high-grade compared to low-grade neuroendocrine neoplasms of the lung; however, this small pilot study failed to show an association between polySia-NCAM expression and response to therapy.