Pulmonary mucinous adenocarcinomas: architectural patterns in correlation with genetic changes, prognosis and survival

Abstract

Of pulmonary adenocarcinomas, about 25-30 % of cases is of a mucinous type. Mucinous adenocarcinomas are regarded as more aggressive compared to their non-mucinous counterparts. Invasive mucinous adenocarcinoma, colloid, and enteric adenocarcinomas are variants within adenocarcinomas. We investigated 76 invasive mucinous adenocarcinomas, including colloid variants, for predominant and secondary patterns, their different form of mucin storage and release, expression of cytokeratin 7 and 20, TTF1 and CDX2, MUC1, 2, and 5AC proteins, p14 and p16 proteins, possible rearrangements for EML4ALK and ROS1, as well as KRAS mutational status, and correlated this with survival. For comparison, 259 non-mucinous adenocarcinomas were selected. Overall survival for invasive mucinous adenocarcinomas corrected for T and N stage was not different from their non-mucinous counterpart. Most were of an acinar pattern. Neither pattern, nor type of mucin storage and release, such as luminal, extracellular, or goblet cell type had any influence on survival. Of adenocarcinomas expressing CK20, all but one expressed TTF1 either strongly or at least focally, and 8 co-expressed CDX2 focally. Most mucinous adenocarcinomas expressed either MUC1 or MUC5AC proteins, but rarely MUC2, while a few cases co-expressed both or all three. Loss of p16 expression correlated with worse outcome. KRAS mutation was found in 56 % of mucinous adenocarcinomas. Mutational status was neither correlated with architectural pattern nor survival. Codon 12 mutations were most frequent, and one case presented with KRAS mutations in codon 12 and 61. Goblet cell variants of mucinous adenocarcinomas presented predominantly with codon 12 mutations, while all colloid variants had KRAS mutation. Two cases had EML4 and ALK1 rearranged; ROS1 rearrangement was not found. Mucinous adenocarcinomas behave similar to non-mucinous variants. TNM stage is the most important factor followed by p16 loss predicting overall survival.

Best Practices Recommendations for Diagnostic Immunohistochemistry in Lung Cancer

“…Given that the differentiation of lung adenocarcinomas with mucinous features (pulmonary mucinous adenocarcinomas) from metastatic lesions is often challenging on a morphologic basis alone, multiple groups have studied the role of IHC in this context. In particular, distinguishing a metastasis from a pancreatic primary from invasive mucinous adenocarcinoma of the lung is far more challenging, given the similar immunoprofiles (focal caudal type homeobox 2 (CDX2) and cytokeratin 20 [ Table 8]) [140][141][142][143][144][145][146][147][148][149][150][151][152][153][154][155][156][157][158][159]161 ; furthermore, a lepidic growth pattern, which is characteristic of invasive mucinous adenocarcinoma (Fig. 12), is also often identified in pancreatic ductal adenocarcinoma metastatic to the lung (Fig.…”

Non-Mucinous Lepidic Predominant Adenocarcinoma Presenting with Extensive Aerogenous Spread

“…2,3,10 The present case showing a poor response to cytotoxic chemotherapy followed by a poor clinical outcome indicates that aerogenous spread may be a prominent factor related to a poor prognosis also in cases of non-mucinous LPAs.…”

Pulmonary enteric adenocarcinoma with pancreatic metastasis: A case report

“…As the studies by Geles et al (17) and Suzuki et al (18) lacked the specific information concerning patients and the results of IHC, these studies were excluded from the analysis. The results of the analysis demonstrated that, in the 41 cases of PEAC recorded, the positive rate of CK7 was 87.8%, the negative rates of CK20 and TTF-1 were 70.7 and 51.2%, respectively, and the positive rate of CDX2 ranged between 51.2 and 65.9% (Table III).…”

“…Indeed, certain patients with primary pancreatic tumors have normal CA19-9 levels; however, if CA19-9 is maintained at a normal level, the possibility of the occurrence of primary pancreatic tumors decreases. Furthermore, it has been Geles et al (17) conducted morphological, IHC and genetic tests on pulmonary mucinous adenocarcinoma; however, the number of PEAC patients and specific results from the IHC tests were not specified, therefore this study is not included. Although Suzuki et al (18) confirmed the number of PEAC cases, only CDX2 was examined, therefore the study was omitted.…”

“…PEAC is a rare pathological type. Between 1 May 2005 and 8 October 2015, <20 PEAC-related references have been recorded by PubMed (www.ncbi.nlm.nih.gov/pubmed) and Wanfang (http://g.wanfangdata.com.cn/) (2,3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”