Morphometric characteristics of cell proliferation and p53 expression in development of experimentally induced respiratory tumors.
OBJECTIVE
To study, under controlled conditions, the applicability of automated image analysis of immunohistochemical markers as an indicator of development and progression in tobacco component-induced tumors in the respiratory tract.


METHODS
Amount, location, size, shape and intensity of staining of proliferating cell and p53 antigen in chemically induced precursors and squamous cell carcinoma of the hamster lung were determined by computer-assisted morphometry.


RESULTS
The total expression of proliferating cell nuclear antigen (PCNA) and p53 expression increased consistently during the formation of papillomas and squamous cell carcinomas of the larynx, trachea, bronchi and lungs. Individual preneoplastic cells in epithelial dysplasia expressed PCNA staining, increasing with increasing cell size and optical density, indicating antibody- staining intensity, in relation to the increased degree of cellular atypia. In malignant tumors, cell size decreased with decreasing differentiation, while antibody staining intensity remained unchanged. The increased alterations in cell shape and percent PCNA-positive cells observed in dysplastic epithelium and squamous cell carcinomas were statistically significant using Spearman's correlation coefficient. Squamous cell carcinomas consisted of two tumor cell populations with different cell shapes, and PCNA and p53 staining intensity. Altering measurement conditions-antibody threshold levels, size of measured area and repeating measurements-showed computer-assisted image analysis to give sensitive, reliable and consistent results.


CONCLUSIONS
Computer-assisted analysis of immunohistochemical staining showed high sensitivity and reproducibility; however, the results depended upon the method of study.
Laitakari
J
J
Department of Pathology, University of Oulu, Finland.
Harrison
D
D
Stenbäck
F
F
D000818:Animals; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D048429:Cell Size; D006224:Cricetinae; D015870:Gene Expression; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007150:Immunohistochemistry; D008647:Mesocricetus; D010212:Papilloma / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D010865:Pilot Projects; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D015203:Reproducibility of Results; D012142:Respiratory Tract Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D012680:Sensitivity and Specificity; D013194:Staining and Labeling; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002227:Carbazoles; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53