Original ContributionsThe P16/cyclin D1/Rb pathway in neuroendocrine tumors of the lung*,☆☆
Section snippets
Patients
Cases were retrieved from the consultation files of the Armed Forces Institute of Pathology and from the Laboratoire de Pathologie Cellulaire, Grenoble. The diagnoses of TC, AC, LCNEC, and SCLC were made using the current World Health Organization/International Association for the Study of Lung Cancer criteria.21 A total of 180 cases (34 TCs, 25 ACs, 42 LCNECs, and 79 SCLCs) were included in the study.
Clinical characteristics of the TC group were as follows: mean age of 49 years (±15); 18 males
Results
The staining results are summarized in Tables 1 through 4.Empty Cell N P16+ P16− N Cyclin D1+ Cyclin D1− N Rb+ Rb− TC 23 21 2 34 2 32 29 29 0 AC 22 17 5 25 5 20 24 19 5 LCNEC 40 31 9 42 4 38 40 13 27 SCLC 75 70 5 79 1 78 77 10 67 Empty Cell Rb− Rb+ P Overall group P16− 8 13 P16+ 90 48 0.017 TC P16− 0 2 − P16+ 0 21 NS AC P16− 2 3 P16+ 3 14 NS LCNEC P16− 3 6 P16+ 24 7 0.013 SCLC P16− 3 2 P16+ 63 6 0.029
Discussion
NE tumors of the lung include a spectrum of tumors from low-grade TCs to intermediate-grade ACs and high-grade LCNECs and SCLCs. Our study demonstrates that the Rb pathway is consistently compromised in LCNECs and SCLCs, less frequently compromised in ACs, and essentially intact in TCs. Abnormalities of the Rb pathway, in the form of p16 loss, cyclin D1 overexpression, or Rb protein loss, were found in 13% of TCs, 59% of ACs, and 92% of both LCNECs and SCLCs. In the 2 high-grade tumors,
Acknowledgements
We thank Marylène Lorinet for typing, Christine Claraz for technical assistance, and Jean-Michel Lasserre for photographic work.
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Supported in part by INSERM, ARC, La Ligue Nationale contre le Cancer (E.B.).
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Address correspondence and reprint requests to Professor Elisabeth Brambilla, Laboratoire de Pathologie Cellulaire, BP 217, 38043 Grenoble Cedex 9, France.