Department of Legal Medicine, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan.
Int J Mol Sci. 2024 Jul 10;25(14):7581. doi: 10.3390/ijms25147581.
This study examined the patterns of epidermal growth-factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) deposition in the small intestine and colon to evaluate the association between the histopathological severity of EFEMP1 deposition and constipation and determine the colocalization of amyloid transthyretin (ATTR) and EFEMP1 deposits. In 40 older cases (≥80 years of age), EFEMP1 deposition in the small intestine initiated in the submucosal and subserous vessels, subserous interstitium, and serosa (early stage), progressing to the muscularis propria and peri-Auerbach plexus area (intermediate stage), and finally spreading diffusely to other areas, excluding the mucosa and muscularis mucosa (advanced stage). The colon had a similar pattern of progression. During the middle-to-advanced stages, amyloid formation was observed in some vascular and serous deposits. A subgroup of cases was identified in which EFEMP1 deposition was the only presumed cause of constipation. Additionally, we demonstrated the colocalization of ATTR and EFEMP1 deposition. Apple-green birefringence was detected under polarized light only in approximately one-half of the cases in the small intestine and one-third of the cases in the colon. These findings strongly suggest that EFEMP1 deposits are correlated with pathological conditions of the lower gastrointestinal tract. As the histopathological diagnosis using Congo red-stained specimens is challenging, the combined use of elastic fiber staining and EFEMP1 immunohistochemistry is recommended to identify EFEMP1 deposition.
本研究检测了表皮生长因子富含纤维连接蛋白样细胞外基质蛋白 1(EFEMP1)在小肠和结肠中的沉积模式,以评估 EFEMP1 沉积的组织病理学严重程度与便秘之间的关联,并确定淀粉样转甲状腺素(ATTR)和 EFEMP1 沉积物的共定位。在 40 例老年病例(≥80 岁)中,EFEMP1 沉积在小肠中首先发生在黏膜下和浆膜下血管、浆膜下间质和浆膜(早期),进展到固有肌层和 Auerbach 神经丛周围区域(中期),最后扩散到其他区域,不包括黏膜和固有肌层(晚期)。结肠也有类似的进展模式。在中晚期,一些血管和浆膜沉积物中观察到淀粉样形成。确定了一个亚组病例,其中 EFEMP1 沉积是便秘的唯一推定原因。此外,我们还证明了 ATTR 和 EFEMP1 沉积的共定位。在偏振光下,仅在小肠的约一半病例和结肠的三分之一病例中检测到苹果绿双折射。这些发现强烈表明 EFEMP1 沉积与下消化道的病理状况有关。由于刚果红染色标本的组织病理学诊断具有挑战性,建议联合使用弹性纤维染色和 EFEMP1 免疫组织化学来识别 EFEMP1 沉积。