1. Early KRAS oncogenic driver mutations in nonmucinous tissue of congenital pulmonary airway malformations as an indicator of potential malignant behavior
- Author
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Rene M. H. Wijnen, Jan H. von der Thüsen, T. Dorine den Toom, Sergei M. Hermelijn, J. Marco Schnater, Robbert J. Rottier, Janina L. Wolf, Pediatric Surgery, and Pathology
- Subjects
0301 basic medicine ,Adult ,Male ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Adolescent ,medicine.disease_cause ,Asymptomatic ,Pathology and Forensic Medicine ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Cystic Adenomatoid Malformation of Lung, Congenital ,Biomarkers, Tumor ,Medicine ,Humans ,CDX2 ,Child ,Lung ,business.industry ,Infant, Newborn ,Infant ,Middle Aged ,medicine.disease ,Adenocarcinoma, Mucinous ,Staining ,030104 developmental biology ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,030220 oncology & carcinogenesis ,Child, Preschool ,Mutation ,Adenocarcinoma ,Immunohistochemistry ,Female ,KRAS ,medicine.symptom ,business ,Airway ,Precancerous Conditions - Abstract
The potential for malignant degeneration is the most common reason for some practitioners to resect asymptomatic congenital pulmonary airway malformations (CPAMs). We aimed to investigate the potential of various immunohistochemical (IHC) and genomic biomarkers to predict the presence of mucinous proliferations (MPs) in CPAM. Archival CPAM tissue samples were re-assessed and underwent IHC analysis using a panel of differentiating markers (TTF1/CDX2/CC10/MUC2/MUC5AC/p16/p53/DICER1). In each sample, intensity of IHC staining was assessed separately in normal lung tissue, CPAM, and MP tissue, using a semiquantitative approach. Likewise, next-generation targeted sequencing of known adult lung driver mutations, including KRAS/BRAF/EGFR/ERBB2, was performed in all samples with MP and in control samples of CPAM tissue without MP. We analyzed samples of 25 CPAM type 1 and 25 CPAM type 2 and found MPs in 11 samples. They were all characterized by strong MUC5AC expression, and all carried a KRAS mutation in the MP and adjacent nonmucinous CPAM tissue, whereas the surrounding normal lung tissue was negative. By contrast, in less than half (5 out of 12) control samples lacking MP, the CPAM tissue also carried a KRAS mutation. KRAS mutations in nonmucinous CPAM tissue may identify lesions with a potential for malignant degeneration and may guide histopathological assessment and patient follow-up.
- Published
- 2020