Department of Pathology and Oregon National Primate Center, Oregon Health and Science University, Portland, OR, USA.
Dig Dis Sci. 2012 Feb;57(2):364-70. doi: 10.1007/s10620-011-1876-7. Epub 2011 Sep 18.
PGP 9.5 is a cytoplasmic protein and is a specific marker for neurites and neurons.
Using anti-PGP 9.5, this study aimed to localize nerve fibers in normal colons, polyps, adenomas and adenocarcinomas.
Colonic polyps, adenomas and T(1) to T(3) adenocarcinomas with adjacent normal colon were immunostained for PGP 9.5 using rabbit anti-PGP 9.5.
In normal colon, numerous nerve fibers were localized in inner and outer muscles, from which submucosa and lamina propria were innervated. In hyperplastic polyps and tubular adenomas, the stalk revealed Meissner's plexus and large-diameter nerve fibers, and fine nerve fibers innervated abundantly in lamina propria of hyperplastic polyps and small tubular adenomas. In villous adenomas, large-diameter nerve fibers and Meissner's plexus were localized in the stalk whereas a few or no fine nerve fibers were localized in fine stroma. In adenocarcinomas, more fine fibers were localized in submucosal stroma adjacent to the invading carcinoma in T(1) carcinomas but there were no nerve fibers in the midst of tumors in T(2) and T(3) carcinomas. There were focally and sporadically increased nerve fibers adjacent to invading cancer nests in 5 of 8 T(2) cases. In T(3) carcinomas, fragmented Auerbach's plexus were noted in cancer-invaded colonic muscles and there were no increased fine nerve fibers in the cancer-invaded subserosa in the majority of cases. PGP 9.5 immunostaining revealed tumor-associated neurogenesis in submucosa but no obviously increased nerve fibers within cancer-invaded muscles.
This lack of tumor-associated neurogenesis supports insidious and often silent clinical presentation of colonic carcinomas until invading through the colonic wall to adjacent organs.
PGP9.5 是一种细胞质蛋白,是神经突和神经元的特异性标志物。
本研究使用抗 PGP9.5 来定位正常结肠、息肉、腺瘤和腺癌中的神经纤维。
使用兔抗 PGP9.5 对结肠息肉、腺瘤和 T1 至 T3 期腺癌及其相邻正常结肠进行 PGP9.5 免疫染色。
在正常结肠中,大量神经纤维定位于内、外肌层,由其向黏膜下层和固有层发出神经纤维。在增生性息肉和管状腺瘤中,蒂部可见 Meissner 丛和大直径神经纤维,增生性息肉和小管状腺瘤固有层中神经纤维丰富分布。在绒毛状腺瘤中,大直径神经纤维和 Meissner 丛定位于蒂部,而在细基质中仅定位少量或无细神经纤维。在腺癌中,T1 期癌旁黏膜下基质中定位于更多的细纤维,但在 T2 和 T3 期癌的肿瘤中部无神经纤维。在 8 例 T2 病例中有 5 例可见邻近侵袭性癌巢的神经纤维呈局灶性和散在性增加。在 T3 期癌中,可见肿瘤侵犯结肠肌肉时 Auerbach 丛呈片段状,而在大多数病例中,肿瘤侵犯的浆膜下区无增加的细神经纤维。PGP9.5 免疫染色显示黏膜下存在肿瘤相关神经生成,但在肿瘤侵犯的肌肉内无明显增加的神经纤维。
这种肿瘤相关神经生成的缺乏支持结直肠癌隐匿且常为无症状的临床表现,直到肿瘤穿透结肠壁侵犯邻近器官。