Lung Adenocarcinoma is the most common type of lung cancer and one of the most dangerous diseases of humankind, which can lead to death if not treated. It accounts for approximately 40-50% of all lung cancers, representing 50-60% of all NSCLC cases. Within this spectrum, approximately one-third differentiate along a mucinous pathway. It has been claimed, that mucinous adenocarcinomas behave worse than their non-mucinous counterpart. Invasive mucinous, colloid, and enteric adenocarcinomas are variants of adenocarcinomas. Between 2002 and 2012 we identified 335 surgically resected cases of mucinous and non-mucinous adenocarcinomas. The aim of the study is to compare the overall survival as well as the progression-free survival of mucinous versus non-mucinous adenocarcinomas of the lung. We also investigated 76 mucinous adenocarcinomas, including colloid variants, for their predominant and secondary patterns, their different form of mucin storage and release, their expression of cytokeratins 7 and 20, TTF1 and CDX2, and MUC1, 2 and 5AC proteins, their expression of p14, and p16 proteins, their possible rearrangements for EML4ALK and ROS1, as well as their KRAS mutational status and correlated this with survival. For comparison 259 non-mucinous adenocarcinomas were selected. The clinical data of Patients with mucinous and non-mucinous adenocarcinoma of the lung were collected retrospectively. The following data also have to be compared considering parameters such as gender, smoking / non-smoking, pack-years, postoperative treatments, chemotherapy, radiotherapy, metastatic profile, and the reason for the death of the patient as a result of the tumour (cancer-related death). Although it is an accepted assumption, that mucinous LUADs if stratified by stage behave more aggressively than their non-mucinous counterparts, cytomorphological and architectural features have not been evaluated and correlated with prognosis and genetic aberrations. Therefore we aim to address these features in 76 cases derived from a single institution. There was a statistically significant difference between T- (log-rank test; P=0.00067) and N-stages (log-rank test; P=0.000073). The corresponding hazard ratio of mucinous carcinoma was 1.31 (95%CI: 0.77 to 2.20). The relative risk of 1 would be neutral. Overall survival of mucinous adenocarcinomas corrected for T and N stage was not different from their non-mucinous counterpart. The acinar pattern was most frequently seen. Neither pattern, nor type of mucin storage, such as luminal, extracellular, or goblet cell type had any influence on survival. There was no difference between mucinous and non-mucinous adenocarcinomas of the lung concerning to survival after adjusting for clinical groups, however, the confidence interval was now 0.63 to 1.83. This contrasts the literature stating that the mucinous have a worse prognosis than the non-mucinous tumours. Several adenocarcinomas were positive for CK20, all of them except one expressed TTF1 either strongly or at least focally, and eight coexpressed CDX2 focally. Most mucinous adenocarcinomas expressed either MUC1 or MUC5AC proteins, rarely MUC2. Some cases coexpressed both or all three. In mucinous adenocarcinomas, a loss of p16 expression correlated with a worse outcome. Mucinous adenocarcinomas exhibit mutation of KRAS oncogene in 56%. KRAS mutational status was neither correlated with architectural pattern nor survival. Most frequent were codon 12 mutations, one case presented with double KRAS mutations in codon 12 and 61. Goblet cell variants of mucinous adenocarcinomas presented predominantly with codon 12 mutations. All colloid variants had KRAS mutation. Two cases had EML4 and ALK1 rearranged, ROS1 rearrangement was not found. Mucinous adenocarcinomas behave similarly to non-mucinous variants. TNM stage is the most important factor followed by p16 loss predicting overall survival.
The influence of various factors on the survival rate of mucinous and non-mucinous lung adenocarcinoma
Geles, A. (Author). 2024
Student thesis: Doctoral thesis