Gradual Histopathologic Changes During Development of Colorectal Cancer

Document Type : Research/Original Article


1 Department of Biology, Faculty of Sciences, Urmia University, Urmia, Iran

2 Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Urmia University of Medical Sciences, Urmia, Iran

3 Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran

4 Department of Pathology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

5 Department of Pathobiology and Quality Control, Artemia and Aquatic Animals Research Institute, Urmia University, Urmia, Iran


Background: Colorectal cancer is one of the most common causes of mortality in the world.
Objectives: The aim of this study was to investigate the histopathologic changes including hyperchromatism, tissue lymphocyte
infiltrations (TILs), aberrant crypt foci (ACF), microvessel density (MVD), p53, Bcl-2 and CD31 changes during colorectal cancer development.
Methods: Subcutaneous injections of dimethyl hydrazine DMH were administered to rats (40 mg/kg body weight) for 10 weeks.
Rats were fed by food and water until 40th week and sacrificed two by two within 10, 15, 20, 25, 30 and 40 weeks after the start of
treatment. Thin paraffinized sections were applied to anti-CD31, anti-Bcl-2 and anti-p53 staining procedures. MVD and ACF were
reported as mean value of three HPFs.
Results: Hyperchromatism, TILs and angiogenesis were the most common initial histologic changes which started at 10th week of
DMH treatment. Hyperchromatism’s severity increased earlier than other changes and reached the highest value at the 25th week.
The highest value of all variants occurred in the 40th week except the TILs which started to achieve the highest value in week 30 and
increased until 40th week. A diminished amount of p53 was observed at week 40, however, increased intensity of CD31 and Bcl-2
were seen between 30th and 40th week.
Conclusions: In conclusion, TILs and angiogenesis might be the important earliest factors contributing to colorectal cancer progression.