FSIP2 can serve as a predictive biomarker for Clear Cell Renal Cell Carcinoma prognosis.

Purpose: To characterize the role of fibrous sheath interacting protein 2 (FSIP2) in the survival outcomes and prognosis of clear cell renal cell carcinoma (ccRCC) patients, which is currently not well understood. Methods: The Oncomine and CCLE databases were used to investigate the differential expression of FSIP2 in ccRCC versus other cancer types. Levels of FSIP2 in 85 ccRCC patients were assessed by immunohistochemical analysis; clinicopathological features related to FSIP2 expression were examined in these patients finally, disease-free survival and overall survival were estimated by survival analysis to elucidate the impact of FSIP2 expression in ccRCC patients. Results: Analysis using the Oncomine database revealed significant upregulation of the FSIP2 gene in papillary RCC, compared to that in normal tissues. Additionally, FSIP2 expression was found to be significantly associated with abnormal platelet count, positive distant metastasis, and death as the incidence of distant metastasis and death were higher in patients with FSIP2 expression compared to those without FSIP2 expression. Survival analysis revealed that FSIP2 expression was significantly related to shorter disease-free survival and overall survival. Meanwhile, patients with FSIP2 expression had worse prognosis than those without FSIP2 expression. Conclusions: FSIP2 expression is associated with poor survival outcomes and poor prognosis in ccRCC patients. FSIP2 may therefore serve as a potential predictive biomarker of ccRCC prognosis.

Immunolocalization of dynein, dynactin, and kinesin in the cerebral tissue as a possible supplemental diagnostic tool for traumatic brain injury in postmortem examination.

Traumatic brain injury (TBI) is characterized by various micro- and macrostructural neuropathological changes which can be identified in the light microscope examination. The most common pathophenotype of TBI visualized in postmortem neuropathological assessment includes neuron injury with involvement of all of its structural regions followed by its progressive degeneration defined as traumatic axonal injury (TAI). This is directly related with disruption of the axolemmal cytoskeletal network architecture resulting in breakdown, dissolution and accumulation of a number of neuronal proteins. Regarding the availability and progress in the development of specific antibodies against neuronal proteins, their usage is restricted due to low specificity for injured axons in the pathomechanism of TBI followed by TAI. Taking this into account with relation to expanding the role of axonal cytoskeleton and its based biomarkers we have presented a study documenting neuropathological features concerning the expression of dynein (DNAH9), dynactin (DCTN1) and kinesin (KIF5B) in the brain specimens obtained during forensic autopsies from TBI victims. The study was carried out using cases (n = 21) of severe head injury suspected to be the cause of death and control cases (n = 17) of sudden death in the mechanism of cardiopulmonary failure along with a positive control case which died after suicidal gunshot injury. In our study, we documented that DNAH9, DCTN1, and KIF5B staining should be considered as a supplemental diagnostic tool for TBI in postmortem neuropathological examination and forensic autopsy. This additional motor protein immunohistochemical staining procedure could be useful in the evaluation of lesions that may remain undiagnosed during a routine examination and aid in more accurate identification of TBI followed by TAI.

Absence or mislocalization of DNAH5 is a characteristic marker for motile ciliary abnormality in nasal polyps.

OBJECTIVE: Motile cilia impairment is a common condition in patients with chronically inflamed airways, such as is seen in nasal polyps (NPs). The mechanism underlying this pathogenic condition is complex and not fully understood. METHODS: We investigated the presence and localization of dynein axonemal heavy chain 5 (DNAH5) in motile cilia using immunofluorescence staining in paraffin-embedded nasal biopsies from NPs (n = 120) and inferior turbinate mucosa (n = 35) of healthy controls. We also performed single-cell staining on cytospin samples (NP = 5, control = 5). Three patterns of DNAH5 localization are defined, including pattern A (presence throughout the axoneme), pattern B (undetectable in the distal part of the axoneme), and pattern C (completely missing throughout the entire axoneme). We developed a semiquantitative scoring system for which 0 = (pattern A > 70%); 1 = (patterns A + B > 70%); and 2 = (pattern C ≥ 30%) in each high-power field (5 fields per sample). RESULTS: Based on our DNAH5 scoring system, the median (1st and 3rd quartile) score was 0.3 (0.2 and 0.4) for samples from controls, and 1.1 (0.6 and 1.6) for samples from NPs in paraffin specimens (P < 0.001). The DNAH5 score had a significant positive relationship with the Lund-Mackay computed tomography score (r = 0.329, P = 0.005) and was higher in patients with eosinophilic NPs (P = 0.006). For cytospin samples, the mean percentage of patterns A, B, and C were 74%, 14%, and 12% in controls, and 48%, 20%, and 32% in NPs, respectively. CONCLUSION: Our results suggest that the absence or mislocalization of DNAH5 from motile cilia is a common and potentially important pathological phenomenon in chronically inflamed airway epithelium. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E97-E104, 2018.