Kit Expression in Small Cell Carcinomas of the Lung: Effects of Chemotherapy

Giulio Rossi, Alberto Cavazza, Alessandro Marchioni, Mario Migaldi, Mario Bavieri, Nicola Facciolongo, Stefano Petruzzelli, Lucia Longo, Stefano Tamberi, Lucio Crinò

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

A significant number of small cell lung carcinomas shows overexpression of the proto-oncogene c-kit product, a tyrosine kinase known as Kit or CD117. This molecular pathway seems somewhat implicated in promoting the neoplastic growth of small ceH lung carcinoma. The current pharmacological availability of its selective inhibitor, together with the promising clinical results in the management of CD117-positive neoplasms such as advanced gastrointestinal stromal tumors, aroused great interest among oncologists in also adopting this therapeutic strategy in other CD117-positive tumors. We evaluated a series of 27 small cell lung carcinomas, comparing the expression of CD117 of the primary naïve tumor (before first-line chemotherapy) with the expression of the same neoplasm after postchemotherapy relapse. All the patients underwent similar chemotherapeutic regimens (cisplatin/carboplatin plus etoposide). At diagnosis, 21 of 27 cases (78%) showed strong immunoreactivity for CD117. Among these 21 originally positive tumors, CD117 remained overexpressed in 10 after relapse (48%), whereas the other 11 cases became negative. No originally CD117-negative small cell carcinomas displayed immunoreactivity after chemotherapy. CD117 expression was not statistically correlated with overall survival, occurrence of chemoresistance, or clinical response to chemotherapy. We also evaluated CD117 expression in a series of 46 surgically resected non-small cell lung carcinomas (8 squamous cell carcinomas, 10 adenocarcinomas, 5 pleomorphic carcinomas, 10 typical and 3 atypical carcinoids, and 10 large cell neuroendocrine carcinomas). Apart from small cell carcinomas, CD117 overexpression was observed in 6 of 10 large cell neuroendocrine carcinomas, whereas all the other histotypes resulted unstained. We speculate that loss of CD117 expression after chemotherapy in a high proportion of SCLC indicates that in this tumor, Kit unlikely represents the product of a constitutive mutation, as instead shown in gastrointestinal stromal tumors. Keeping this finding in mind, oncologists could re-test CD117 expression in relapsing small cell lung carcinomas in order to establish the best candidates for enrollment in ongoing clinical trials with Kit inhibitors. Practically speaking, CD117 may be helpful in discriminating between pulmonary high-grade neuroendocrine tumors and other histotypes, but pathologists should be aware that treated small cell lung carcinomas may remain unstained in a not insignificant number of cases.

Original languageEnglish
Pages (from-to)1041-1047
Number of pages7
JournalModern Pathology
Volume16
Issue number10
DOIs
Publication statusPublished - Oct 2003

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Small Cell Lung Carcinoma
Drug Therapy
Neuroendocrine Carcinoma
Large Cell Carcinoma
Neoplasms
Gastrointestinal Stromal Tumors
Small Cell Carcinoma
Carcinoma
Recurrence
Lung
Neuroendocrine Tumors
Proto-Oncogenes
Carboplatin
Carcinoid Tumor
Etoposide
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Cisplatin
Squamous Cell Carcinoma
Adenocarcinoma

Keywords

  • c-kit Immunohistochemistry
  • CD117
  • Lung
  • Small cell carcinoma
  • STI571

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Rossi, G., Cavazza, A., Marchioni, A., Migaldi, M., Bavieri, M., Facciolongo, N., ... Crinò, L. (2003). Kit Expression in Small Cell Carcinomas of the Lung: Effects of Chemotherapy. Modern Pathology, 16(10), 1041-1047. https://doi.org/10.1097/01.MP.0000089780.30006.DE

Kit Expression in Small Cell Carcinomas of the Lung : Effects of Chemotherapy. / Rossi, Giulio; Cavazza, Alberto; Marchioni, Alessandro; Migaldi, Mario; Bavieri, Mario; Facciolongo, Nicola; Petruzzelli, Stefano; Longo, Lucia; Tamberi, Stefano; Crinò, Lucio.

In: Modern Pathology, Vol. 16, No. 10, 10.2003, p. 1041-1047.

Research output: Contribution to journalArticle

Rossi, G, Cavazza, A, Marchioni, A, Migaldi, M, Bavieri, M, Facciolongo, N, Petruzzelli, S, Longo, L, Tamberi, S & Crinò, L 2003, 'Kit Expression in Small Cell Carcinomas of the Lung: Effects of Chemotherapy', Modern Pathology, vol. 16, no. 10, pp. 1041-1047. https://doi.org/10.1097/01.MP.0000089780.30006.DE
Rossi, Giulio ; Cavazza, Alberto ; Marchioni, Alessandro ; Migaldi, Mario ; Bavieri, Mario ; Facciolongo, Nicola ; Petruzzelli, Stefano ; Longo, Lucia ; Tamberi, Stefano ; Crinò, Lucio. / Kit Expression in Small Cell Carcinomas of the Lung : Effects of Chemotherapy. In: Modern Pathology. 2003 ; Vol. 16, No. 10. pp. 1041-1047.
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abstract = "A significant number of small cell lung carcinomas shows overexpression of the proto-oncogene c-kit product, a tyrosine kinase known as Kit or CD117. This molecular pathway seems somewhat implicated in promoting the neoplastic growth of small ceH lung carcinoma. The current pharmacological availability of its selective inhibitor, together with the promising clinical results in the management of CD117-positive neoplasms such as advanced gastrointestinal stromal tumors, aroused great interest among oncologists in also adopting this therapeutic strategy in other CD117-positive tumors. We evaluated a series of 27 small cell lung carcinomas, comparing the expression of CD117 of the primary na{\"i}ve tumor (before first-line chemotherapy) with the expression of the same neoplasm after postchemotherapy relapse. All the patients underwent similar chemotherapeutic regimens (cisplatin/carboplatin plus etoposide). At diagnosis, 21 of 27 cases (78{\%}) showed strong immunoreactivity for CD117. Among these 21 originally positive tumors, CD117 remained overexpressed in 10 after relapse (48{\%}), whereas the other 11 cases became negative. No originally CD117-negative small cell carcinomas displayed immunoreactivity after chemotherapy. CD117 expression was not statistically correlated with overall survival, occurrence of chemoresistance, or clinical response to chemotherapy. We also evaluated CD117 expression in a series of 46 surgically resected non-small cell lung carcinomas (8 squamous cell carcinomas, 10 adenocarcinomas, 5 pleomorphic carcinomas, 10 typical and 3 atypical carcinoids, and 10 large cell neuroendocrine carcinomas). Apart from small cell carcinomas, CD117 overexpression was observed in 6 of 10 large cell neuroendocrine carcinomas, whereas all the other histotypes resulted unstained. We speculate that loss of CD117 expression after chemotherapy in a high proportion of SCLC indicates that in this tumor, Kit unlikely represents the product of a constitutive mutation, as instead shown in gastrointestinal stromal tumors. Keeping this finding in mind, oncologists could re-test CD117 expression in relapsing small cell lung carcinomas in order to establish the best candidates for enrollment in ongoing clinical trials with Kit inhibitors. Practically speaking, CD117 may be helpful in discriminating between pulmonary high-grade neuroendocrine tumors and other histotypes, but pathologists should be aware that treated small cell lung carcinomas may remain unstained in a not insignificant number of cases.",
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