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

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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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Addendum

A recently published study by Shim et al. focused also on a similar cohort of mucinous adenocarcinomas. The authors found similar survival data as well as a high prevalence of KRAS mutations, thus confirming our findings. Importantly they had significantly low mutations in TP53, which raises the question which proteins other than p53 cooperates with p16 (J.Thoracic Oncol. 2015 Aug;10(8):1156-62).

Conflict of interest

This investigation was in part supported by an unrestricted grant from Hofman La Roche to HHP. No conflict of interest is to be declared in connection with this study.

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  1. Abidin Geles

    Present address: Department of Surgery, University of Zuerich, Zuerich, Switzerland

Authors and Affiliations

  1. Department of Surgery, Division of Thoracic and Hyperbaric Surgery, Medical University of Graz, Graz, Austria

    Abidin Geles & Freyja Juettner-Smolle

  2. Institute of Pathology Teaching Hospital Feldkirch, Feldkirch, Austria

    Ulrike Gruber-Moesenbacher

  3. Institute for Medical Informatics, Statistics and Documentation Medical University of Graz, Graz, Austria

    Franz Quehenberger

  4. Institute of Pathology Medical University Innsbruck, Innsbruck, Austria

    Claudia Manzl

  5. Institute of Pathology, Research Unit Molecular Lung and Pleura Pathology, Medical University of Graz, Graz, Austria

    Mohamed Al Effah, Elisabeth Grygar & Helmut H. Popper

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  1. Abidin Geles
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Correspondence to Helmut H. Popper.

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Geles, A., Gruber-Moesenbacher, U., Quehenberger, F. et al. Pulmonary mucinous adenocarcinomas: architectural patterns in correlation with genetic changes, prognosis and survival. Virchows Arch 467, 675–686 (2015). https://doi.org/10.1007/s00428-015-1852-2

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