CD117 immunoreactivity in stage I adenocarcinoma and squamous cell carcinoma of the lung: relevance to prognosis in a subset of adenocarcinoma patients

Abstract

CD117, a trans-membrane tyrosine kinase receptor, has been immunolocalized in a large variety of human neoplasms. Little, however, is known about the prevalence and clinical implications of CD117 in stage I adenocarcinoma and squamous cell carcinoma of the lung. We evaluated 201 consecutive stage I adenocarcinoma and squamous cell carcinoma of the lung for CD117 immunoreactivity (dichotomized as negative or positive if containing less than 5% or Z5% immunoreactive neoplastic cells, respectively), also taking into account the pattern (either membranous or cytoplasmic), and the intensity of immunostaining in comparison with intratumoral mast cells. The immunostaining results were then correlated with tumor biopathological characteristics and patients' survival. Membranous CD117 immunoreactivity was documented in 19 (22%) of 88 adenocarcinomas and 15 (13%) of 113 squamous cell carcinomas, whereas cytoplasmic labelling was seen in 28 (32%) adenocarcinomas and eight (7%) squamous cell carcinomas. In both tumor types, membranous or cytoplasmic CD117 immunoreactivity was associated with higher proliferative fraction and with features of more aggressive tumor behavior, including higher stage, size and grade, occurrence of clinical symptoms, high microvessel density and neuroendocrine differentiation. Furthermore, immunoreactive tumors exhibited increased levels of bcl-2, cyclin-E, Her-2, p27Kip1 and fascin, the latter being a marker of tumor cell metastatization in lung cancer. Membranous but not cytoplasmic labelling emerged as an independent risk factor for death and reduced time to progression in adenocarcinoma but not in squamous cell carcinoma patients, when singly adjusted for confounding factors. CD117 immunoreactivity identifies a peculiar subset of stage I adenocarcinoma and squamous cell carcinoma of the lung with highly proliferative tumors and may have prognostic relevance in adenocarcinoma patients. Targeting the CD117 pathway could be a novel therapeutic strategy in a subset of pulmonary carcinomas.

CD117 immunoreactivity in high-grade neuroendocrine tumors of the lung: a comparative study of 39 large-cell neuroendocrine carcinomas and 27 surgically resected small-cell carcinomas

“…A cytoplasmic labeling for this molecule, however, has been reported by others in several tumor types, including small-cell carcinomas [17,20,27], large-cell neuroendocrine carcinomas [8], non-small-cell carcinomas of the lung [3,25], colorectal neuroendocrine carcinoma [1], and gastrointestinal stromal tumors [10]. Moreover, definite paranuclear, dotlike, cytoplasmic immunoreactivity for CD117 is also common in gastrointestinal tumor cells [10], and a definite nuclear immunolocalization was reported [18] in both normal and neoplastic medullary cells of the adrenal gland, suggesting that CD117 differs in compartmentalization between the various normal and neoplastic cells.…”

Genomic Alterations in Pulmonary Adenocarcinoma In Situ in an Adolescent Patient

“…NBR1, or neighbor of Low copy number gains in the KIT gene locus on chromosome 4 were also present. KIT mutations and copy number gains have been described in both acral malignant melanomas and stage I lung adenocarcinomas, 12,13 observations that are particularly interesting in light of this patient's history of melanoma.…”

Genomic profiling of small-cell lung cancer: the era of targeted therapies

“…The overexpression of c-KIT is frequently observed in SCLC (25)(26)(27)(28)(29). Three studies examining imatinib have been performed in patients with advanced SCLC.…”