1. Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University. The 52th of Meihua East Road, Zhuhai 519000, China
2. Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-sen University. The 107th of Yanjiang West Road, GuangZhou 510120, China.
3. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center. The 651th of Dongfeng Road, GuangZhou 510060, China
4. Department of Gastroenterology, Lihuili Hospital of Ningbo Medical Center, The 57th of Xingning Road, Ningbo 315040, China
* These authors contributed equally to this work.
Objectives: Tumor-associated macrophages (TAMs) are thought to be involved in the perineural invasion (PNI) process and to be associated with poor prognoses. The associations between TAMs, PNI, and clinicopathological features in pancreatic ductal adenocarcinomas (PDAs) remain to be elucidated. Methods: Fifty-nine PDA patients who had undergone pancreaticoduodenectomy were retrospectively examined. The PNI statuses and TAMs were reviewed following H&E staining and S-100, CD68, and CD163 immunohistochemical staining. The relationships between PNI, TAMs, and overall survival and various clinical and histopathologic factors were investigated. Results: PNI was identified in 83% (49/59) of the cases, the TAM density of the PNI+ group was greater than that of the PNI- group, and the infiltrating TAMs around the nerves that were invaded by cancer were much more numerous than those around the nerves without cancer cell invasion. The incidences of PNI, lymph node metastasis, high serum CA19-9 level, cancers in the body/tail, and advanced pathological stage were associated with shorter OSs. In the PNI+ group, lymph node metastasis and high levels of TAM infiltration were associated with worse prognoses. Conclusions: TAMs might enhance PNI, and the incidence of PNI was associated with poor prognosis. PNI+ status and high levels of TAM infiltration further worsen the prognosis. Therapies targeting TAMs might represent auxiliary and preventive treatment for PNI in PDA patients.
Keywords: pancreatic ductal adenocarcinomas, perineural invasion, tumor associated macrophages, immunohistochemical, lymph node metastasis.