Presence of microscopic skipping growth pattern correlated with KRAS or GNAS mutations in pulmonary mucinous adenocarcinoma

Abstract

Introduction

Mucinous adenocarcinoma is a special subtype of non-small cell lung carcinoma (NSCLC). Currently, it remains unclear whether the molecular alterations are associated with its clinicopathological characteristics.

Methods

A total of 93 cases of pulmonary mucinous adenocarcinoma were assessed in this study. DNA and RNA sequencing were performed and clinical pathological characteristics were collected. Correlation analyses were conducted to explore associations between molecular alterations, pathological features, and clinical outcomes.

Results

The KRAS mutation frequency was 49 %. The group with KRAS mutations had low to intermediate nuclear grade (p < 0.001), microscopic skip lesions (p = 0.005), and a lower proportion of patients with vascular invasion (p = 0.030). While vascular invasion (p = 0.044), intermediate to high nuclear grade, especially high nuclear grade (p = 0.007), and tumors with a maximum diameter greater than 4 cm (p = 0.012) were commonly observed in patients with TP53 mutations, which also was correlated with a shorter time to progression (TTP).

Conclusions

In this study, we found that mucinous adenocarcinomas of the lung with KRAS mutations tended to be pure-type mucinous adenocarcinomas with low to intermediate-grade nuclei, microscopic skip lesions, and the absence of vascular invasion. Tumors with TP53 mutations tended to be larger in size and exhibit higher nuclear grade as well as frequent vascular invasion. These morphological features may suggest that the tumor is accompanied by some kind of molecular alteration. If this is found in the puncture biopsy specimen, the patient may be advised to undergo molecular testing with a view to finding a suitable targeted agent for treatment.