Objective: To investigate significance of the Lewy pathology in biopsy and surgical specimen in the gastrointestinal (GI) tract as an in-vivo biomarker for Parkinson disease (PD).

Background: Alpha-synuclein (AS) immunohistochemistry (IHC) of the GI tract biopsy is considered as a promising pathologic biomarker for PD. However, this promise has not been substantiated by comparing the pathologic findings of biopsy with those of surgically resected full-depth specimen.

Methods: We conducted a case-control study in patients with PD who underwent radical operation in the GI tract for treatment of cancer. The controls were matched with age at operation, gender, and location of the surgical specimen. Patients and controls were further categorized as the stomach or colorectal group by location of the specimen. If available, biopsied tissue from routine clinical practice within 1 year before the operation was collected. We performed phosphorylated AS (pAS) IHC in the upper and lower marginal blocks of the surgical specimen and biopsied tissue.

Results: Total 33 patients with PD and 33 matched controls were included in this study. Twelve patients were categorized as the stomach group and 21 as the colorectal group. Biopsied tissues were available in 22 (66.7%) patients and 22 (66.7%) controls. The frequency of pAS immunoreactivity in the surgical specimen was only 7/12 (58.3%) in patients of the stomach group, which was  significantly higher than that of the matched controls (1/12 [8.3%]; p=0.027); and was only 5/21 (23.8%) in the colorectal group, which was the same in the control group (5/21 [23.8%]). The frequency of pAS immunoreactivity in the biopsied tissue was not different between patients and controls (2/22 [9.1%] vs 4/22 [18.2%]; p=0.664). Furthermore, pAS immunoreactivity in the biopsied tissue was not concordant with that in the surgical specimen.

Conclusions: In our study with the surgically resected specimen which is full depth and much larger than biopsy, pAS immunoreactivity was only 58.3% and 23.8% in the stomach and colorectal specimen, respectively. Therefore, current strategy for searching a pathologic biomarker of PD using pAS IHC on the biopsied tissues from the GI tract will inevitably suffer low positive rate and lack of specificity which is supported by poor concordance between biopsy and surgical specimen.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/fundamental-limit-of-the-alpha-synuclein-immunohistochemistry-using-the-endoscopic-biopsy-from-the-gastrointestinal-tract-as-a-biomarker-for-parkinson-disease-a-case-control-study/