Kohoutova Darina, Pejchal Jaroslav, Bures Jan
Charles University, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, 2nd Department of Internal Medicine - Gastroenterology, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
University of Defence, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.
BMC Gastroenterol. 2018 May 18;18(1):65. doi: 10.1186/s12876-018-0786-y.
Colorectal cancer (CRC) is third most commonly diagnosed cancer worldwide. The aim of the prospective study was to evaluate mitosis and apoptosis of epithelial cells at each stage of colorectal neoplasia.
A total of 61 persons were enrolled into the study: 18 patients with non-advanced colorectal adenoma (non-a-A), 13 patients with advanced colorectal adenoma (a-A), 13 patients with CRC and 17 controls: individuals with normal findings on colonoscopy. Biopsy samples were taken from pathology (patients) and healthy mucosa (patients and healthy controls). Samples were formalin-fixed paraffin-embedded and stained with haematoxylin-eosin. Mitotic and apoptotic activity were evaluated in lower and upper part of the crypts and in the superficial compartment. Apoptotic activity was also assessed using detection of activated caspase-3.
In controls, mitotic activity was present in lower part of crypts, accompanied with low apoptotic activity. Mitotic and apoptotic activity decreased (to almost zero) in upper part of crypts. In superficial compartment, increase in apoptotic activity was observed. Transformation of healthy mucosa into non-a-A was associated with significant increase of mitotic activity in lower and upper part of the crypts and with significant increase of apoptotic activity in all three compartments; p < 0.05. Transformation of non-a-A into a-A did not lead to any further significant increase in apoptotic activity, but was related to significant increase in mitotic activity in upper part of crypts and superficial compartment. A significant decrease in apoptotic activity was detected in all three comparments of CRC samples compared to a-A; p < 0.05. No differences in mitotic and apoptotic activity between biopsies in healthy controls and biopsy samples from healthy mucosa in patients with colorectal neoplasia were observed. Detection of activated caspase-3 confirmed the above findings in apoptotic activity.
Significant dysregulation of mitosis and apoptosis during the progression of colorectal neoplasia, corresponding with histology, was confirmed. In patients with sporadic colorectal neoplasia, healthy mucosa does not display different mitotic and apoptotic activity compared to mucosa in healthy controls and therefore adequate endoscopic/surgical removal of colorectal neoplasia is sufficient.
结直肠癌（CRC）是全球第三大常见诊断癌症。这项前瞻性研究的目的是评估结直肠肿瘤各阶段上皮细胞的有丝分裂和凋亡情况。
共有61人纳入本研究：18例非进展期结直肠腺瘤患者（非进展期腺瘤，non-a-A），13例进展期结直肠腺瘤患者（进展期腺瘤，a-A），13例结直肠癌患者以及17名对照：结肠镜检查结果正常的个体。从病理标本（患者）和健康黏膜（患者及健康对照）获取活检样本。样本经福尔马林固定、石蜡包埋，并用苏木精-伊红染色。在隐窝的下部和上部以及表层区域评估有丝分裂和凋亡活性。还通过检测活化的半胱天冬酶-3评估凋亡活性。
在对照组中，有丝分裂活性存在于隐窝下部，伴有低凋亡活性。隐窝上部的有丝分裂和凋亡活性降低（几乎为零）。在表层区域，观察到凋亡活性增加。健康黏膜转变为非进展期腺瘤与隐窝下部和上部有丝分裂活性显著增加以及所有三个区域凋亡活性显著增加相关；p < 0.05。非进展期腺瘤转变为进展期腺瘤并未导致凋亡活性进一步显著增加，但与隐窝上部和表层区域有丝分裂活性显著增加有关。与进展期腺瘤相比，结直肠癌样本的所有三个区域均检测到凋亡活性显著降低；p < 0.05。未观察到健康对照的活检与结直肠肿瘤患者健康黏膜活检样本之间有丝分裂和凋亡活性的差异。活化半胱天冬酶-3的检测证实了上述凋亡活性的结果。
证实了结直肠肿瘤进展过程中有丝分裂和凋亡的显著失调，与组织学情况相符。在散发性结直肠肿瘤患者中，健康黏膜与健康对照的黏膜相比，未表现出不同的有丝分裂和凋亡活性，因此对结直肠肿瘤进行充分的内镜/手术切除就足够了。
