SRSF‐1 and microvessel density immunohistochemical analysis by semi‐automated tissue microarray in prostate cancer patients with diabetes (DIAMOND study)

Abstract

Objective: To study the association between insulin receptors (isoforms α and β), insulin growth factor-1 (IGF1) and serine/arginine splicing factor 1 (SRSF-1) in patients with prostate cancer (PC) and diabetes. Materials and Methods:We retrospectively analyzed data from 368 patients who underwent surgery for PC or benign prostatic hyperplasia (BPH) between 2010 and 2020 at the Department of Urology, University of Catania. Tissue microarray slides were constructed and they were stained for androgen receptor (AR), insulin receptor-α and -β, IGF1 (IGF1-R), Ki-67, and prostate specific membrane antigen (PSMA) expression using validated score. Results:The final cohort was represented by 100 patients with BPH and 268 with PC, with a median age of 68 years. We found that SRSF-1 expression was associated

Prognostic Value of the Immunohistochemical Expression of Serine and Arginine-Rich Splicing Factor 1 (SRSF1) in Uveal Melanoma: A Clinico-Pathological and Immunohistochemical Study on a Series of 85 Cases

“…SRSF1 is an RNA-binding protein with proto-oncogenic function, being involved in angiogenesis, cell migration and tumor proliferation of several types of human neoplasms, including gliomas, malignant mesotheliomas, and breast, colorectal and prostate cancers [18,[20][21][22][23][24][25]. SRSF1 immunoexpression was positively associated with worse outcome, androgen-receptor status and Ki-67 proliferation rate in prostatic adenocarcinoma [27]; a significant correlation between SRSF1, MVD and shorter overall survival times was also found in fluoro-edenite-induced malignant mesothelioma [26]. In the present paper we provided the first immunohistochemical evidence of the poor prognostic role of this protein in UM; in more detail, we found a statistically significant correlation between higher SRSF1 immunohistochemical expression, higher MVD levels and poorer prognosis in terms of metastatic spread and lower metastasis-free-survival in UM.…”

“…Regarding the relationship between SRSF1 and MVD, previous studies demonstrated that SRSF1 had a stimulatory function on tumor angiogenesis, resulting in a switch in the pro-angiogenic/anti-angiogenic ratio of VEGFA [17][18][19][20][21]; in this regard, Barbagallo et al first reported the complex relationship between circSMARCA5, a specific subtype of circRNAs with a tumor-suppressor role, and SRSF1, demonstrating that the downregulation of circSMARCA5 along with the concomitant upregulation of SRSF1 led to increased cell migration and angiogenesis in human glioblastoma tissue and cell lines [17][18][19]. The MVD count, despite not representing the best method to evaluate tumor angiogenesis, is a semi-quantitative "surrogate" of this process [27]; accordingly, the positive correlation found in our cohort between SRSF1 and MVD led us to hypothesize that SRSF1 has a pro-angiogenic role also in UM.…”

“…Immunohistochemical analyses were performed as previously described [26][27][28]; briefly, standard and appropriate deparaffinization and pre-treatments were performed; subsequently, the sections were incubated for 30 min at 37 • C with mouse monoclonal anti-SRSF1 antibody (sc-33652; working dilution 1:50; Santa Cruz Biotechnology; Dallas, TX, USA) and with mouse monoclonal anti-CD31 antibody (JC70A; working dilution 1:40; DAKO, Glostrup, Denmark). The presence of brown chromogen within tumor nuclei was interpreted as positive SRSF1 immunohistochemical staining; non-pathologic gallbladder mucosa was used as positive control, while negative control slides were obtained by incubating them with phosphate-buffered saline instead of the primary antibody.…”

“…The presence of brown chromogen within tumor nuclei was interpreted as positive SRSF1 immunohistochemical staining; non-pathologic gallbladder mucosa was used as positive control, while negative control slides were obtained by incubating them with phosphate-buffered saline instead of the primary antibody. UM cases stained with SRSF1 were semi-quantitatively analyzed, as previously described [26][27][28]: the Intensity of Staining (IS) was evaluated on a 0-3 scale (mild, moderate and strong), while the Extent Score (ES) (the percentage of positive cells) on a 0-4 scale (<5%; 5-30%; 31-50%; 51-75%; >75%). We obtained the Immunoreactivity Score (IRS) by multiplying IS and ES, and considered the immunohistochemical expression of SRSF1 as low if IRS was ≤6 (L-IRS), and as high if IRS >6 (H-IRS).…”

“…In this regard, it has been suggested that SRSF1 tends to promote the formation of the pro-angiogenic isoform of VEGFA, instead of the anti-angiogenic one [17][18][19][20][21]. Consistent with its stimulatory role on tumor angiogenesis, SRSF1 has been found overexpressed in several human neoplasms, including prostate, brain, breast, colorectal, liver, pleural and lung tumors [20,[22][23][24][25][26][27]; however, to the best of our knowledge, no data on the role of this protein in UM are present in literature to date.…”