PINK1 Immunoexpression Predicts Survival in Patients Undergoing Hepatic Resection for Colorectal Liver Metastases.

PTEN-induced kinase-1 (PINK1) is the initiator of the canonical mitophagy pathway. Our aim was to study the immunoexpression of PINK1 in surgical specimens from ninety patients with metastatic colorectal adenocarcinoma (CRC) to the liver (CRLM). Tissue arrays were produced, and immunohistochemical studies were analyzed by the H-Score method. The mean immunoexpression of PINK1 in normal tissues was between 40 to 100 points. In tumoral tissues, positive PINK1 immunoexpression was observed in all samples, and no differences were noted between CRCs. In CRLMs, a significant under-expression was noted for PINK1 from the rectum (71.3 ± 30.8; p < 0.042) compared to other sites. Altered PINK1 immunoexpression in CRCs, either higher than 100 points or lower than 40 points, was associated with worse overall survival (OS) (p < 0.012) due to a shorter post-metastatic survival (PMS) (p < 0.023), and it was found to be a significant independent predictor of prognosis in a multivariate model for OS and PMS (HR = 1.972, 95% CI 0.971-4.005; p = 0.022. HR = 2.023, 95% CI 1.003-4.091; p = 0.037, respectively). In conclusion, altered PINK1 immunoexpression determined in CRCs with resected CRLM predicts a worse prognosis, possibly due to the abnormal function of mitophagy.

Extradural en-plaque spinal lipomatous meningioma: A case report and literature review.

BACKGROUND: Extradural spinal meningiomas are rare, and few appear as lipomatous meningiomas in an "en-plaque" form. The transitional fibroblastic subtype, with lipid accumulation within the tumoral cells, is typically more aggressive and surgically challenging to resect. CASE DESCRIPTION: A 42-year-old male presented with neck pain and progressive paresthesias in both upper extremities. Based on the radiological findings, the tentative preoperative diagnosis was lymphoma. However, the biopsy confirmed a meningioma. The patient underwent a combined extradural anterior and posterior approach, resulting in full tumor resection. Histopathologically, the final report documented a lipomatous meningioma. CONCLUSION: Extradural spinal lipomatous meningiomas (i.e., "en-plaque") are rare and typically result in rapid clinical deterioration. The radiological diagnosis may be difficult, while ultrasonography helps to define their extradural location facilitating planning for gross total anterior/posterior excision where indicated.

Upregulated Expression of Heparanase and Heparanase 2 in the Brains of Alzheimer's Disease.

BACKGROUND: Heparan sulfate proteoglycans (HSPGs) promote amyloid-ß peptide and tau fibrillization in Alzheimer's disease (AD) and provide resistance against proteolytic breakdown. Heparanase (HPSE) is the only enzyme that cleaves heparan sulfate (HS). Heparanase 2 (HPSE2) lacks HS-degrading activity, although it is able to interact with HS with high affinity. OBJECTIVE: To analyze HPSE and HPSE2 expressions at different stages of AD. METHODS: RT-PCR was used to analyze transcription levels of both heparanases at different stages of AD, and immunohistochemistry was performed to localize each one in different parts of the brain. RESULTS: Both proteins appeared overexpressed at different stages of AD. Immunohistochemistry indicated that the presence of the heparanases was related to AD pathology, with intracellular deposits found in degenerated neurons. At the extracellular level, HPSE was observed only in neuritic plaques with a fragmented core, while HPSE2 appeared in those with compact cores as well. CONCLUSION: Given the involvement of HSPGs in AD pathology, there would seem to be a relationship between the regulation of heparanase expression, the features of the disease, and a possible therapeutic alternative.