The role of claudin 18.2 and HER-2 in pancreatic cancer outcomes

Abstract

To examine the prognostic value of claudin 18.2 (CLDN18.2) and human epidermal growth factor receptor-2 (HER-2) expression in patients with resected pancreatic ductal adenocarcinoma (PDAC). This study enrolled patients who underwent surgery and were diagnosed with PDAC at Suleyman Demirel University Hospital, Turkey between 2015 and 2019. Sixty-eight patients with resected PDAC treated at a medical oncology clinic were assessed. All patients were over the age of 18 years, underwent follow-up and treatment in our unit, and had pathology slides that we could access. Clinicopathological data were obtained from medical files, including the patients’ age, sex, pathological parameters, and clinical stage according to the Eighth International Union against Cancer/American Joint Committee on Cancer. Patient survival and the period from the date of diagnosis to death were assessed in the follow-up data. There was no statistically significant difference between CLDN18.2 and HER-2 expression scores for samples and patient clinicopathological characteristics. No HER-2 expression scores of ≥2 were found in the samples. Only 25% (n = 17) of the samples had HER-2 expression scores of +1. CLDN18.2 expression was detected in 54.4% (n = 37) of the patient samples. CLDN18.2 expression scores were +1 in 30.8% (n = 21) of the patient samples, +2 in 16.2% (n = 11), and +3 in 7.4% (n = 5). When CLDN18.2 and HER-2 expression were compared, a statistically significant difference and moderate positive correlation were observed. No significant relationship between HER-2 expression and survival was observed in the survival analysis of PDAC patients; however, high CLDN18.2 expression was related to longer overall survival. Our study is the third to research CLDN18.2 expression in PDAC. HER-2 expression is low and CLDN18.2 expression is high in patients with PDAC. HER-2 expression is not related to overall survival but CLDN18.2 is related and may be used as a prognostic marker in patients with PDAC.

Extent and clinical significance of the therapy-relevant tight junction protein Claudin 18.2 in pancreatic ductal adenocarcinoma - real-world evidence

“…Previous studies, which investigated the expression of Claudin 18.2 in PDAC showed higher expression rates [ 14 , 21 , 22 ]. However, other studies showed expression rates, that align with our study [ 9 , 20 ]. These differences could be explained by the use of various antibodies and cut-off values for CLDN18.2 positivity.…”

“…We also found that Claudin 18.2 was an independent factor for favorable prognosis in patients with PDAC (HR = 0.686, 95 % CI = 0.492–0.956, p = 0.026). Supporting our findings, Kayikcioglu et al report a significant correlation between patients with high Claudin 18.2 expression and better overall survival in a patient cohort of sixty-eight patients [ 20 ]. On the contrary, high Claudin 18.2 expression was correlated with lymph node and distant metastases as well as poor patient survival [ 22 ].…”

“…Previous studies showed inconsistent results regarding the influence of Claudin 18.2 on patients’ survival in PDAC [ 9 , 20 ]. Therefore, we performed survival analyses comparing the overall survival of patients with negative and positive Claudin 18.2 expression.…”

“…All in all, analytical comparability of the LSBio antibody with the in clinical trials used VENTANA assay can be assumed, which has played an established role in Claudin 18.2 detection. Notably, the studies mentioned above of Claudin 18.2 expression levels in patients with PDAC did not use the VENTANA CLDN18 Assay or LSBio antibody but used distinct antibodies by Abcam and Invitrogen which were not explored in the previously mentioned ring study regarding their reliability [ 9 , 11 , 20 , 22 ]. Moreover, different findings between Claudin 18.2 overexpression and patient survival could be explained by a common problem of analyses of immunohistochemical stainings.…”

“…Moreover, different findings between Claudin 18.2 overexpression and patient survival could be explained by a common problem of analyses of immunohistochemical stainings. Various cut-offs for the definition of positive Claudin 18.2 stainings were used in previous studies investigating Claudin 18.2 positivity in PDAC (≥ 75 % of tumor cells and staining intensities of ≥ 2+, staining intensity solely, and median H-Score) [ 9 , 20 , 22 ]. Nevertheless, we used the definition (positive staining in ≥75 % of tumor cells and staining intensities of ≥ 2+), which is used in phase III trials evaluating the newly introduced antibody Zolbetuximab in combination with established therapy options [ 6 , 7 ].…”