Apoptotic activity is increased in parallel with the metaplasia-dysplasia-carcinoma sequence of the bronchial epithelium.

Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print Cited Medium: Print ISSN: 0007-0920 (Print) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE

Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK
Original Publication: London, Lewis.

Apoptosis*; Bronchi/*pathology ; Carcinoma in Situ/*pathology ; Carcinoma, Squamous Cell/*pathology ; Lung Neoplasms/*pathology ; Precancerous Conditions/*pathology; Biomarkers, Tumor/analysis ; Bronchi/cytology ; DNA Fragmentation ; Epithelial Cells/cytology ; Epithelium/pathology ; Humans ; Immunohistochemistry ; Metaplasia ; Myeloid Cell Leukemia Sequence 1 Protein ; Neoplasm Proteins/analysis ; Proto-Oncogene Proteins/analysis ; Proto-Oncogene Proteins c-bcl-2/analysis ; Reference Values ; Retrospective Studies ; Tumor Suppressor Protein p53/analysis ; bcl-2-Associated X Protein

A high level of apoptotic activity and an independence of apoptosis from the expression of p53 and bcl-2 have been observed in non-small-cell lung carcinoma. We examined 44 samples of normal, metaplastic and premalignant (i.e. mild, moderate and severe dysplasias and carcinoma in situ) bronchial epithelia to evaluate whether differences in the apoptotic activity could already be seen in the stages preceding squamous cell carcinoma of the lung (SQCLC). Apoptotic cells and bodies were visualized by 3' end labelling. The expression of p53 and members of the bcl-2 gene family, such as bcl-2, bax and mcl-1, were determined immunohistochemically with specific antibodies. The relative number of apoptotic cells and bodies [apoptotic index (AI%)] was already increased threefold as the normal bronchial epithelium changed to squamous metaplasia, and the AIs of the dysplastic lesions were about four times higher than those of the normal epithelium. Apoptosis was significantly associated with cell proliferation, as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry. However, the extent of apoptosis did not correlate with the expression of p53, bcl-2, bax and mcl-1. We conclude that, in the metaplasia-dysplasia-carcinoma sequence in the lung, the elevation of the AI% is an early event associated with cell proliferation activity, but is independent of the expression of p53, bcl-2, mcl-1 and bax.

Science. 1997 Feb 21;275(5303):1129-32. (PMID: 9027314)
Cancer Res. 1994 Sep 15;54(18):4855-78. (PMID: 8069852)
Am J Clin Pathol. 1995 Mar;103(3):300-7. (PMID: 7872252)
Science. 1994 Nov 4;266(5186):807-10. (PMID: 7973635)
Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):6961-5. (PMID: 1871110)
Nat Med. 1997 Jun;3(6):614-20. (PMID: 9176486)
Oncogene. 1992 Oct;7(10):1989-97. (PMID: 1408139)
Am J Pathol. 1994 Feb;144(2):296-302. (PMID: 7906095)
Br J Cancer. 1997;75(3):367-73. (PMID: 9020481)
Br J Cancer. 1994 Aug;70(2):297-303. (PMID: 7914423)
Lancet. 1992 Mar 7;339(8793):576-80. (PMID: 1347094)
Cancer Res. 1993 Oct 15;53(20):4817-22. (PMID: 8402667)
Cancer. 1995 Jan 15;75(2):522-9. (PMID: 7529128)
Cell Death Differ. 1995 Jul;2(3):173-82. (PMID: 17180040)
Cancer. 1996 Jan 15;77(2):255-64. (PMID: 8625232)
Br J Cancer. 1972 Aug;26(4):239-57. (PMID: 4561027)
Br J Cancer. 1996 May;73(9):1025-30. (PMID: 8624258)
Cell. 1997 Feb 7;88(3):355-65. (PMID: 9039262)
Br J Cancer. 1997;76(2):175-9. (PMID: 9231916)
J Pathol. 1994 Aug;173(4):333-9. (PMID: 7965393)
Eur J Cancer. 1994;30A(14):2068-73. (PMID: 7857705)
Nature. 1997 Jan 23;385(6614):353-7. (PMID: 9002522)
J Cell Biol. 1994 Jan;124(1-2):1-6. (PMID: 8294493)
Am J Pathol. 1993 Mar;142(3):725-32. (PMID: 8456936)
Cancer Res. 1995 Jan 15;55(2):215-9. (PMID: 7812946)
N Engl J Med. 1979 Feb 22;300(8):381-5. (PMID: 759914)
N Engl J Med. 1957 Jan 17;256(3):97-104. (PMID: 13388038)
Cell. 1996 Jun 14;85(6):817-27. (PMID: 8681377)
Virchows Arch A Pathol Anat Histopathol. 1992;421(5):415-20. (PMID: 1333678)
J Pathol. 1995 May;176(1):37-44. (PMID: 7616355)
J Pathol. 1996 Nov;180(3):275-82. (PMID: 8958805)
Cancer Res. 1992 Nov 1;52(21):6079-82. (PMID: 1394234)
Virchows Arch. 1996 Jul;428(4-5):229-35. (PMID: 8764931)
Science. 1984 Nov 30;226(4678):1097-9. (PMID: 6093263)
Br J Cancer. 1995 Jul;72(1):164-9. (PMID: 7599047)
Cancer Res. 1995 Dec 1;55(23):5595-602. (PMID: 7585640)
Eur J Cancer B Oral Oncol. 1995 Nov;31B(6):380-3. (PMID: 8746268)
Cell. 1985 Jul;41(3):899-906. (PMID: 3924412)
J Urol. 1996 Jan;155(1):316-20. (PMID: 7490878)
J Pathol. 1993 Apr;169(4):431-7. (PMID: 8501540)
N Engl J Med. 1962 Jul 19;267:111-9. (PMID: 13863213)
Cell. 1993 Aug 27;74(4):609-19. (PMID: 8358790)
J Pathol. 1997 Feb;181(2):172-7. (PMID: 9120721)

0 (BAX protein, human)
0 (Biomarkers, Tumor)
0 (Myeloid Cell Leukemia Sequence 1 Protein)
0 (Neoplasm Proteins)
0 (Proto-Oncogene Proteins)
0 (Proto-Oncogene Proteins c-bcl-2)
0 (Tumor Suppressor Protein p53)
0 (bcl-2-Associated X Protein)

Date Created: 19990310 Date Completed: 19990325 Latest Revision: 20181113

20231215

PMC2362669

10.1038/sj.bjc.6690159

10070903