Volume 28, Issue 1 (3-2021)
RJMS 2021, 28(1): 55-63 |
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Zare-Mirzaie A, Achak F, Babaheidarian P. Evaluating relation of CD133 expression in colorectal adenocarcinoma and clinicopathlogic findings. RJMS 2021; 28 (1) :55-63
URL: http://rjms.iums.ac.ir/article-1-6212-en.html
URL: http://rjms.iums.ac.ir/article-1-6212-en.html
Iran University of Medical Sciences, Tehran, Iran , pegibh@gmail.com
Abstract: (2359 Views)
Background & Aims: Colon cancer is among the four most prevalent cancers and the second lethal cancer in the world. After proposing of cancer stem cell hypothesis in recent years numerous studies have been done on various tumor markers with the aim of finding a molecule characterizing the cancer stem cell having prognostic and probably therapeutic value. Cancer stem cell model is well known nowadays which emphasize only small number of tumor cells could initiate tumor growth and maintain its own population.Multiple stem cell markers such as CD44, CD24, SOX2, OCT4, are introduced,among which CD133 has more or less shown this property in different kinds of cancers. CD133 is a glycoprotein which is produced by hematopoietic cells, glial cells and colorectal cancers. Tumor cells with expression of CD133 on their surface lose their special character but have strong epithelial adhesion molecule, recent studies have shown that CD133-positive colorectal cancer cells are a major trigger for this type of cancer; but the results are contradictory as to whether these cells are the same cancer stem cells. The expression of this marker may be associated with a poor prognosis, but its association with metastasis is unknown. The aim of this study was to determine the relationship between this tumor marker and clinical pathological findings, to clarify its role in tumor formation, spread and metastasis. In addition, this marker can be used as a potential pharmacological target in the treatment of cancer patients.
Methods: First, the pathology archive of Rasoul Akram Hospital was investigated and the clinical and pathological information related to the pathology files and reports of patients with colorectal cancer who underwent colon resection surgery in this hospital from 1390 to 1396 were extracted. The aim of this study was to evaluate the expression of CD133 marker in NOS adenocarcinoma. Therefore, in order to standardize the test conditions of patients with non-epithelial tumors, mucinous and ring cell carcinoma tumors were excluded from the study. Also, patients with rectosigmoid carcinoma who underwent neoadjuvant chemotherapy before surgery were excluded from the study due to its effect on the nature of cancer cells. Tumor location in patients was divided into two groups. Tumors located in the proximal to the middle of the transverse colon were called right colon tumors and distal tumors were called left colon tumors. Tumor size was entered as the largest tumor diameter in centimeters. Since pathology reports were prepared by three other pathologists during the mentioned years, in order to standardize the study conditions of patients' slides in terms of depth of tumor invasion, lymph node involvement, degree of tumor differentiation, vascular invasion and perineural invasion was reviewed by a pathologist and, if necessary, slides were prepared from the relevant paraffin blocks. During the examination of the slides, an area with an approximate area of one square centimeter was identified with a marker in the part of the tumor that was located in the invasive front. Human retina was placed on a slide as a positive control. Then, according to the instructions of the marker manufacturer and standard immunohistochemical staining methods, IHC slides were prepared. In the light microscopy, the entire surface of the slides was examined for the color of the marker. According to previous studies, a 5% cut offwas used for this purpose, so that if more than 5% of tumor cells were positive for the above marker, the patient was positive, and if less than this amount was positive, or if no cells were positive, the tumor was reported negative.
Results: Among the 137 patients surveyed, 28 patients (20.4%) were positive for CD133 and 109 patients (79.4%) were negative. In this study, the staining of this marker was luminal and membrane, and as a result, no tumor with poor differentiation was positive. The mean age of patients with CD133 positive tumor was 61.2 16 16.2 years and in negative tumors was 57.2 16 16.3 years. There was no significant relationship. P-value: 0.28: In this study, 76 male patients And 61 were women. Among men, 15 were positive for markers and 61 were negative, and among women, 13 were positive and 48 were negative. There was no statistically significant relationship between patients' sex and the incidence of 133 CDs (= 0.83). The mean of the largest tumor diameter was 4.7 2 1.2 cm in CD133 positive tumors and 5.2 2 2.2 cm in CD133 negative tumors. Among the tumors located on the left, 22 were positive for CD133 and the remaining 83 were negative. Also, among the tumors located on the right colon, 6 tumors were positive for CD133 and 26 were negative, and in general, there was not significant relationship between the tumor site and marker. Apart from the degree of histological differentiation, no statistically significant relationship was found between any of the other clinical-pathological findings and the expression of this marker.
Conclusion: In our study, like some other researchers, but not all tumors with poor differentiation were negative in terms of the expression of markers, which could be explained by the low frequency of glandular structures and lumen formation in such tumors. Our study in comparison with other studies on the relationship between CD133 and clinical-pathological findings of colorectal cancer can show similarities and differences, four studies have found a significant relationship between tumor depth and the expression of this marker. In our study, if we compare T1 + T2 tumors with T3 + t4 tumors, the p-value for this relationship will be 0.07. It seems that if the samples in this study had a larger volume in each group, this relationship would be significant. In other words, the presence of small samples in the group of tumors with low invasive depth and also the presence of small samples in the group with high invasion Due to the lack of surgery in this group, the number of samples in each group was not enough and may be the cause of lack of relationship with some clinical pathological findings.
Methods: First, the pathology archive of Rasoul Akram Hospital was investigated and the clinical and pathological information related to the pathology files and reports of patients with colorectal cancer who underwent colon resection surgery in this hospital from 1390 to 1396 were extracted. The aim of this study was to evaluate the expression of CD133 marker in NOS adenocarcinoma. Therefore, in order to standardize the test conditions of patients with non-epithelial tumors, mucinous and ring cell carcinoma tumors were excluded from the study. Also, patients with rectosigmoid carcinoma who underwent neoadjuvant chemotherapy before surgery were excluded from the study due to its effect on the nature of cancer cells. Tumor location in patients was divided into two groups. Tumors located in the proximal to the middle of the transverse colon were called right colon tumors and distal tumors were called left colon tumors. Tumor size was entered as the largest tumor diameter in centimeters. Since pathology reports were prepared by three other pathologists during the mentioned years, in order to standardize the study conditions of patients' slides in terms of depth of tumor invasion, lymph node involvement, degree of tumor differentiation, vascular invasion and perineural invasion was reviewed by a pathologist and, if necessary, slides were prepared from the relevant paraffin blocks. During the examination of the slides, an area with an approximate area of one square centimeter was identified with a marker in the part of the tumor that was located in the invasive front. Human retina was placed on a slide as a positive control. Then, according to the instructions of the marker manufacturer and standard immunohistochemical staining methods, IHC slides were prepared. In the light microscopy, the entire surface of the slides was examined for the color of the marker. According to previous studies, a 5% cut offwas used for this purpose, so that if more than 5% of tumor cells were positive for the above marker, the patient was positive, and if less than this amount was positive, or if no cells were positive, the tumor was reported negative.
Results: Among the 137 patients surveyed, 28 patients (20.4%) were positive for CD133 and 109 patients (79.4%) were negative. In this study, the staining of this marker was luminal and membrane, and as a result, no tumor with poor differentiation was positive. The mean age of patients with CD133 positive tumor was 61.2 16 16.2 years and in negative tumors was 57.2 16 16.3 years. There was no significant relationship. P-value: 0.28: In this study, 76 male patients And 61 were women. Among men, 15 were positive for markers and 61 were negative, and among women, 13 were positive and 48 were negative. There was no statistically significant relationship between patients' sex and the incidence of 133 CDs (= 0.83). The mean of the largest tumor diameter was 4.7 2 1.2 cm in CD133 positive tumors and 5.2 2 2.2 cm in CD133 negative tumors. Among the tumors located on the left, 22 were positive for CD133 and the remaining 83 were negative. Also, among the tumors located on the right colon, 6 tumors were positive for CD133 and 26 were negative, and in general, there was not significant relationship between the tumor site and marker. Apart from the degree of histological differentiation, no statistically significant relationship was found between any of the other clinical-pathological findings and the expression of this marker.
Conclusion: In our study, like some other researchers, but not all tumors with poor differentiation were negative in terms of the expression of markers, which could be explained by the low frequency of glandular structures and lumen formation in such tumors. Our study in comparison with other studies on the relationship between CD133 and clinical-pathological findings of colorectal cancer can show similarities and differences, four studies have found a significant relationship between tumor depth and the expression of this marker. In our study, if we compare T1 + T2 tumors with T3 + t4 tumors, the p-value for this relationship will be 0.07. It seems that if the samples in this study had a larger volume in each group, this relationship would be significant. In other words, the presence of small samples in the group of tumors with low invasive depth and also the presence of small samples in the group with high invasion Due to the lack of surgery in this group, the number of samples in each group was not enough and may be the cause of lack of relationship with some clinical pathological findings.
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