Decreased immunoreactivity of CD99 is an independent predictor of regional lymph node metastases in pulmonary carcinoid tumors

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Abstract

BACKGROUND: Few data are available on the prevalence and clinicopathological meaning of CD99, the transmembrane product of the pseudoautosomal MIC2 gene, in pulmonary neuroendocrine tumors. METHODS: We evaluated CD99 immunoreactivity in lung tissues, pulmonary neuroendocrine hyperplasias, and 136 consecutive pulmonary neuroendocrine tumors of diverse histological types. RESULTS: By immunohistochemistry, a membranous and/or cytoplasmic immunoreactivity was seen in 60 of 136 (44%) tumors, whereas both normal and hyperplastic neuroendocrine cells of the lung were consistently nonreactive. A steady decrease of the CD99 labeling index was observed from better to poorly differentiated tumors, with a prevalence of the membranous pattern in typical carcinoids (TCs), and of the cytoplasmic pattern in atypical carcinoids (ACs) and large cell neuroendocrine carcinoma/small cell lung carcinoma (P <0.0001), independent of tumor stage. In TCs/ACs, increased levels of CD99 labeling index or the membranous pattern were associated with low proliferative fraction (P = 0.0011) and smaller tumor size (P = 0.0054) and with lack of regional lymph node metastases (P = 0.0078). Moreover, CD99 expression decreased according to the pN0-2 classes (P = 0.0016), with an inverse relationship between the number of positive lymph nodes, the labeling index (P = 0.013) and the nonmembranous pattern (P = 0.016). At multivariate analysis, both the decreased CD99 labeling index and the negative/cytoplasmic staining were independent risk indicators for lymph node metastases in the subset of TC/AC patients. No relevant relationships were found in large cell neuroendocrine carcinoma/small cell lung carcinoma. CONCLUSION: CD99 is especially present in low- to intermediate-grade neuroendocrine tumors of the lung, and loss of the marker correlates with the occurrence of nodal metastases in TC/AC patients.

Original languageEnglish
Pages (from-to)468-477
Number of pages10
JournalJournal of Thoracic Oncology
Volume1
Issue number5
DOIs
Publication statusPublished - Jun 2006

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Carcinoid Tumor
Lymph Nodes
Neoplasm Metastasis
Lung
Neuroendocrine Tumors
Neuroendocrine Carcinoma
Large Cell Carcinoma
Small Cell Lung Carcinoma
Neoplasms
Negative Staining
Neuroendocrine Cells
Hyperplasia
Multivariate Analysis
Immunohistochemistry
Genes

Keywords

  • Carcinoid
  • CD99
  • Lung
  • Metastasis

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Medicine(all)

Cite this

@article{3338dc567da848df9217585cfb256e64,
title = "Decreased immunoreactivity of CD99 is an independent predictor of regional lymph node metastases in pulmonary carcinoid tumors",
abstract = "BACKGROUND: Few data are available on the prevalence and clinicopathological meaning of CD99, the transmembrane product of the pseudoautosomal MIC2 gene, in pulmonary neuroendocrine tumors. METHODS: We evaluated CD99 immunoreactivity in lung tissues, pulmonary neuroendocrine hyperplasias, and 136 consecutive pulmonary neuroendocrine tumors of diverse histological types. RESULTS: By immunohistochemistry, a membranous and/or cytoplasmic immunoreactivity was seen in 60 of 136 (44{\%}) tumors, whereas both normal and hyperplastic neuroendocrine cells of the lung were consistently nonreactive. A steady decrease of the CD99 labeling index was observed from better to poorly differentiated tumors, with a prevalence of the membranous pattern in typical carcinoids (TCs), and of the cytoplasmic pattern in atypical carcinoids (ACs) and large cell neuroendocrine carcinoma/small cell lung carcinoma (P <0.0001), independent of tumor stage. In TCs/ACs, increased levels of CD99 labeling index or the membranous pattern were associated with low proliferative fraction (P = 0.0011) and smaller tumor size (P = 0.0054) and with lack of regional lymph node metastases (P = 0.0078). Moreover, CD99 expression decreased according to the pN0-2 classes (P = 0.0016), with an inverse relationship between the number of positive lymph nodes, the labeling index (P = 0.013) and the nonmembranous pattern (P = 0.016). At multivariate analysis, both the decreased CD99 labeling index and the negative/cytoplasmic staining were independent risk indicators for lymph node metastases in the subset of TC/AC patients. No relevant relationships were found in large cell neuroendocrine carcinoma/small cell lung carcinoma. CONCLUSION: CD99 is especially present in low- to intermediate-grade neuroendocrine tumors of the lung, and loss of the marker correlates with the occurrence of nodal metastases in TC/AC patients.",
keywords = "Carcinoid, CD99, Lung, Metastasis",
author = "Giuseppe Pelosi and Leon, {Maria Elena} and Giulia Veronesi and Lorenzo Spaggiari and Felice Pasini and Giuseppe Viale",
year = "2006",
month = "6",
doi = "10.1097/01243894-200606000-00015",
language = "English",
volume = "1",
pages = "468--477",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "Elsevier Inc.",
number = "5",

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TY - JOUR

T1 - Decreased immunoreactivity of CD99 is an independent predictor of regional lymph node metastases in pulmonary carcinoid tumors

AU - Pelosi, Giuseppe

AU - Leon, Maria Elena

AU - Veronesi, Giulia

AU - Spaggiari, Lorenzo

AU - Pasini, Felice

AU - Viale, Giuseppe

PY - 2006/6

Y1 - 2006/6

N2 - BACKGROUND: Few data are available on the prevalence and clinicopathological meaning of CD99, the transmembrane product of the pseudoautosomal MIC2 gene, in pulmonary neuroendocrine tumors. METHODS: We evaluated CD99 immunoreactivity in lung tissues, pulmonary neuroendocrine hyperplasias, and 136 consecutive pulmonary neuroendocrine tumors of diverse histological types. RESULTS: By immunohistochemistry, a membranous and/or cytoplasmic immunoreactivity was seen in 60 of 136 (44%) tumors, whereas both normal and hyperplastic neuroendocrine cells of the lung were consistently nonreactive. A steady decrease of the CD99 labeling index was observed from better to poorly differentiated tumors, with a prevalence of the membranous pattern in typical carcinoids (TCs), and of the cytoplasmic pattern in atypical carcinoids (ACs) and large cell neuroendocrine carcinoma/small cell lung carcinoma (P <0.0001), independent of tumor stage. In TCs/ACs, increased levels of CD99 labeling index or the membranous pattern were associated with low proliferative fraction (P = 0.0011) and smaller tumor size (P = 0.0054) and with lack of regional lymph node metastases (P = 0.0078). Moreover, CD99 expression decreased according to the pN0-2 classes (P = 0.0016), with an inverse relationship between the number of positive lymph nodes, the labeling index (P = 0.013) and the nonmembranous pattern (P = 0.016). At multivariate analysis, both the decreased CD99 labeling index and the negative/cytoplasmic staining were independent risk indicators for lymph node metastases in the subset of TC/AC patients. No relevant relationships were found in large cell neuroendocrine carcinoma/small cell lung carcinoma. CONCLUSION: CD99 is especially present in low- to intermediate-grade neuroendocrine tumors of the lung, and loss of the marker correlates with the occurrence of nodal metastases in TC/AC patients.

AB - BACKGROUND: Few data are available on the prevalence and clinicopathological meaning of CD99, the transmembrane product of the pseudoautosomal MIC2 gene, in pulmonary neuroendocrine tumors. METHODS: We evaluated CD99 immunoreactivity in lung tissues, pulmonary neuroendocrine hyperplasias, and 136 consecutive pulmonary neuroendocrine tumors of diverse histological types. RESULTS: By immunohistochemistry, a membranous and/or cytoplasmic immunoreactivity was seen in 60 of 136 (44%) tumors, whereas both normal and hyperplastic neuroendocrine cells of the lung were consistently nonreactive. A steady decrease of the CD99 labeling index was observed from better to poorly differentiated tumors, with a prevalence of the membranous pattern in typical carcinoids (TCs), and of the cytoplasmic pattern in atypical carcinoids (ACs) and large cell neuroendocrine carcinoma/small cell lung carcinoma (P <0.0001), independent of tumor stage. In TCs/ACs, increased levels of CD99 labeling index or the membranous pattern were associated with low proliferative fraction (P = 0.0011) and smaller tumor size (P = 0.0054) and with lack of regional lymph node metastases (P = 0.0078). Moreover, CD99 expression decreased according to the pN0-2 classes (P = 0.0016), with an inverse relationship between the number of positive lymph nodes, the labeling index (P = 0.013) and the nonmembranous pattern (P = 0.016). At multivariate analysis, both the decreased CD99 labeling index and the negative/cytoplasmic staining were independent risk indicators for lymph node metastases in the subset of TC/AC patients. No relevant relationships were found in large cell neuroendocrine carcinoma/small cell lung carcinoma. CONCLUSION: CD99 is especially present in low- to intermediate-grade neuroendocrine tumors of the lung, and loss of the marker correlates with the occurrence of nodal metastases in TC/AC patients.

KW - Carcinoid

KW - CD99

KW - Lung

KW - Metastasis

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U2 - 10.1097/01243894-200606000-00015

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