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Published in: Virchows Archiv 6/2015

01-12-2015 | Original Article

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

Authors: Abidin Geles, Ulrike Gruber-Moesenbacher, Franz Quehenberger, Claudia Manzl, Mohamed Al Effah, Elisabeth Grygar, Freyja Juettner-Smolle, Helmut H. Popper

Published in: Virchows Archiv | Issue 6/2015

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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.
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Metadata
Title
Pulmonary mucinous adenocarcinomas: architectural patterns in correlation with genetic changes, prognosis and survival
Authors
Abidin Geles
Ulrike Gruber-Moesenbacher
Franz Quehenberger
Claudia Manzl
Mohamed Al Effah
Elisabeth Grygar
Freyja Juettner-Smolle
Helmut H. Popper
Publication date
01-12-2015
Publisher
Springer Berlin Heidelberg
Published in
Virchows Archiv / Issue 6/2015
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-015-1852-2

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