MUC6 distribution in the spectrum of pulmonary mucinous adenocarcinoma

We read with great interest the insightful and investigative paper by Kishikawa et al. recently published in the Journal 1 Kishikawa S Hayashi T Saito T et al. Diffuse expression of MUC6 defines a distinct clinicopathological subset of pulmonary invasive mucinous adenocarcinoma. Mod Pathol. 2021; 34: 786-797 Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar , which delt with the distribution of membrane-bound (MUC1, MUC4) and secretory (MUC2, MUC5AC, MUC6) mucins in a consecutive series of 70 pulmonary invasive mucinous adenocarcinoma (IMA). We congratulate Authors for the sake of clarity and scientific sound of their paper, whose main conclusions, well reflected in the title, are that MUC6 expression is likely to define a distinct subset of tumors with their own specific clinicopathologic traits and genetic alterations 1 Kishikawa S Hayashi T Saito T et al. Diffuse expression of MUC6 defines a distinct clinicopathological subset of pulmonary invasive mucinous adenocarcinoma. Mod Pathol. 2021; 34: 786-797 Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar . The article is worth mentioning not only for its inherent scientific value of well-conducted piece of research, but also because it confirms our previously reported observations dating back to 2017 on the same subject, where we reappraised under a similar experimental design the spectrum of pulmonary adenocarcinomas with mucin production, including 12 IMA and 15 invasive colloid adenocarcinomas, as basket categories deriving from distinct domains of stem/progenitor cells or local influence areas along bronchioles according to different mucin (MUC1, MUC2, MUC5AC, MUC6) and nuclear transcription factor (CDX-2, TTF1, HNF4-alpha) immunohistochemistry, clinical and demography traits, and common genetic traits 2 Sonzogni A Bianchi F Fabbri A et al. Pulmonary adenocarcinoma with mucin production modulates phenotype according to common genetic traits: a reappraisal of mucinous adenocarcinoma and colloid adenocarcinoma. J Pathol Clin Res. 2017; 3: 139-152 Crossref PubMed Scopus (20) Google Scholar . Our original splitting approach 2 Sonzogni A Bianchi F Fabbri A et al. Pulmonary adenocarcinoma with mucin production modulates phenotype according to common genetic traits: a reappraisal of mucinous adenocarcinoma and colloid adenocarcinoma. J Pathol Clin Res. 2017; 3: 139-152 Crossref PubMed Scopus (20) Google Scholar , which is different from the lumper interpretation provided by the World Health Classifications 3 Editorial Board: Borczuk C, Cooper W, Dacic S, et al. Thoracic tumours. Vol 5. 5th ed. International Agency for Research on Cancer - Lyon (France): 2021. Google Scholar 4 Travis WD Brambilla E Nicholson AG et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 2015; 10: 1243-1260 Abstract Full Text Full Text PDF PubMed Scopus (2711) Google Scholar , has been confirmed by this commendable study on pulmonary IMA 1 Kishikawa S Hayashi T Saito T et al. Diffuse expression of MUC6 defines a distinct clinicopathological subset of pulmonary invasive mucinous adenocarcinoma. Mod Pathol. 2021; 34: 786-797 Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar , just because it unravels diverse phenotypic-genotypic events linked to the inherent heterogeneity of cell differentiation lineages and, potentially, offers strategies of therapy 5 Cha YJ Shim HS Biology of invasive mucinous adenocarcinoma of the lung. Transl Lung Cancer Res. 2017; 6: 508-512 Crossref PubMed Scopus (46) Google Scholar . The respectful statement by the Authors that “this is the first study cohort to assess the association between mucin expression and various clinicopathological and molecular parameters in IMA” 1 Kishikawa S Hayashi T Saito T et al. Diffuse expression of MUC6 defines a distinct clinicopathological subset of pulmonary invasive mucinous adenocarcinoma. Mod Pathol. 2021; 34: 786-797 Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar is however partial, although results of either study 1 Kishikawa S Hayashi T Saito T et al. Diffuse expression of MUC6 defines a distinct clinicopathological subset of pulmonary invasive mucinous adenocarcinoma. Mod Pathol. 2021; 34: 786-797 Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar 2 Sonzogni A Bianchi F Fabbri A et al. Pulmonary adenocarcinoma with mucin production modulates phenotype according to common genetic traits: a reappraisal of mucinous adenocarcinoma and colloid adenocarcinoma. J Pathol Clin Res. 2017; 3: 139-152 Crossref PubMed Scopus (20) Google Scholar converge on the same conclusion that there is a clinicopathological relevance to this investigative approach in mucin-laden pulmonary adenocarcinomas.