P56.04 Pathological Features & Prognosis of NSCLC Patients With Enteric Adenocarcinomas Without Expression of TTF-1 and Napsin A

Abstract

Enteric differentiation can occur in lung adenocarcinoma, and when this component exceeds 50%, the tumor is classified as pulmonary adenocarcinoma with enteric differentiation (PAED). The enteric pattern of enteric lung adenocarcinoma shares morphologic and immunohistochemical features with colorectal adenocarcinoma and it consists of glandular and/or papillary structures sometimes with a cribriform pattern, lined by tumor cells that are mostly tall-columnar with nuclear pseudostratification, luminal necrosis, and prominent nuclear debris. Poorly differentiated tumors may have a more solid pattern. These tumors show at least one immunohistologic marker of enteric differentiation (CDX-2, CK20 or MUC2). Enteric adenocarcinoma is a rare histologic type of primary lung adenocarcinoma. Detailed clinical, pathological and molecular features about these subgroup of patients is lacking, particularly if TTF-1 and Napsin A aren't expressed. NSCLC patients who were diagnosed from January 2018 until March 2021 were identified by review of the patient records. Only lung adenocarcinoma patients whose tumors didn`t express either TTF-1 or Napsin A, but were positive for either CDX-2, CK20 or MUC2 were included in the data analysis. Primary tumor of the gastrointestinal tract was excluded either by PET-CT and/or CT and endoscopy (gastroscopy, colonoscopy, and rectoscopy). A total of fourteen (eight male (57,1%) and six female (42,9%) patients were identified in the patients` records. On average, the patients were 67 years old, the median age was 68. The youngest patient was 54 and the oldest one was 83 years old. Three patients were diagnosed at local stages (I-III), eleven patients had metastatic disease (stage IV). Four of these eleven patients had a mutation of the KRAS gene, which corresponds to 37%. This percentage is higher than the average frequency of mutations in the KRAS gene in pulmonary adenocarcinomas (25%). Half of the patients had a tumors with protein expression of PD-L1 (50%). Four patients of the complete cohort underwent surgical resection of the primary tumor and five patients received radiotherapy. Every patient, who got radiotherapy, suffered from stage IV. Three patients received irradiation of brain metastasis and two of bone metastasis. A systemic therapy was administered to nine patients. Seven patients had a combined chemo-/ immuntherapy as firstline treatment (either cisplatin, pemetrexed, and pembrolizumab or carboplatin, nab-paclitaxel, and atezolizumab) and one got only a combination chemotherapy (carboplatin and nab-paclitaxel). Median disease-free survival was eight, median progression-free survival was four months. Median overall survival could not be calculated. However, six and twelve months survival rates were 35.8 and 25.0 %, respectively. This is the far largest reported series of PAED patients without any expression of TTF1- or Napsin A. It seems that this subgroup of pulmonary adenocarcinoma patients has a poorer prognosis compared to other patients with lung adenocarcinomas.