Browsing by Subject "MAJOR SIALOPROTEIN"

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  • Heby, Margareta; Karnevi, Emelie; Elebro, Jacob; Nodin, Björn; Eberhard, Jakob; Saukkonen, Kapo; Hagström, Jaana; Mustonen, Harri; Seppänen, Hanna; Haglund, Caj; Jirstrom, Karin; Larsson, Anna H. (2020)
    The outcome of periampullary adenocarcinomas remains poor with few treatment options. Podocalyxin-like protein (PODXL) is an anti-adhesive protein, the high expression of which has been shown to confer a poor prognosis in numerous malignancies. A correlation and adverse prognostic synergy between PODXL and the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer. Here, we investigated whether this also applies to periampullary adenocarcinomas. We analyzed the immunohistochemical expression of PODXL and EGFR in tissue microarrays with tumors from two patient cohorts; (Cohort 1, n=175) and (Cohort 2, n=189). The effect of TGF-beta -induced expression and siRNA-mediated knockdown of PODXL and EGFR, were investigated in pancreatic cancer cells (PANC-1) in vitro. We found a correlation between PODXL and EGFR in these cancers, and a synergistic adverse effect on survival. Furthermore, silencing PODXL in pancreatic cancer cells resulted in the down-regulation of EGFR, but not vice versa. Consequently, these findings suggest a functional link between PODXL and EGFR, and the potential combined utility as biomarkers possibly improving patient stratification. Further studies examining the mechanistic basis underlying these observations may open new avenues of targeted treatment options for subsets of patients affected by these particularly aggressive cancers.
  • Eurola, Annika; Ristimäki, Ari; Mustonen, Harri; Nurmi, Anna-Maria; Hagström, Jaana; Haglund, Caj; Seppänen, Hanna (2021)
    Podocalyxin overexpression associates with poor survival in pancreatic cancer (PDAC). We investigated whether podocalyxin expression correlates with treatment response or survival in neoadjuvant-treated PDAC. Through immunohistochemistry, we evaluated podocalyxin expression in 88 neoadjuvant and 143 upfront surgery patients using two antibodies. We developed a six-tier grading scheme for neoadjuvant responses evaluating the remaining tumor cells in surgical specimens. Strong podocalyxin immunopositivity associated with poor survival in the patients responding poorly to the neoadjuvant treatment (HR 4.16, 95% CI 1.56-11.01, p=0.004), although neoadjuvant patients exhibited generally low podocalyxin expression (p=0.017). Strong podocalyxin expression associated with perineural invasion (p=0.003) and lack of radiation (p=0.036). Two patients exhibited a complete neoadjuvant response, while a strong neoadjuvant response (