Prognostic impact of stromal periostin expression in upper urinary tract urothelial carcinoma

Abstract

Background Periostin is an extracellular matrix protein that has been known to be implicated in fibrillogenesis and cell migration, including cancer metastasis. Periostin overexpression in cancer cells and/or intervening stroma is usually related to tumor progression and poor patient outcomes in various human cancers; however, its role in urothelial carcinoma, especially upper urinary tract urothelial carcinomas (UTUCs), remains inconclusive. Methods Samples from 126 consecutive cases of invasive UTUC (69 renal pelvic cancers and 57 ureteral cancers) were histologically reviewed and analyzed for periostin expression using immunohistochemistry. The intensities of immunoreactivity and the fraction of positive cancer cells and stroma (i.e., epithelial and stromal expression, respectively) were classified into four categories each (intensity, 0–3; fraction, 0–25% = 1; 26–50% = 2; 51–75% = 3; and > 75% = 4). The overall score was determined by multiplying both scores, and overall scores ≥ 6 were considered to indicate high periostin expression. Results Among 126 UTUCs, 55 (44%; 27 renal pelvic and 28 ureteral cancers) showed high stromal periostin expression. None of the cases were considered to have high epithelial periostin expression. High stromal periostin expression was associated with non-papillary gross findings, higher pathological T category, lymphovascular invasion, concomitant carcinoma in situ, subtype histology, lymph node metastasis, positive surgical margins, high tumor budding, and high tumor-associated immune cell status. Multivariate analysis revealed that high stromal periostin expression was an independent predictor of overall survival (p = 0.00072, hazard ratio = 3.62), and lymphovascular invasion and high stromal periostin expression were independent predictors of cancer-specific survival (p = 0.032 and 0.020, hazard ratio = 2.61 and 3.07, respectively). Conclusions Stromal periostin expression was often observed in invasive UTUCs with adverse clinicopathological factors and may be a useful predictor of patient outcomes.

Canine urothelial carcinoma: expression of Periostin in spontaneous canine urothelial carcinoma and its correlation with histological features

“…This is an interesting finding and could reflect what was noted in our samples that had a generally weak or absent expression of POSTN but in which an intense ring of POSTN was visible around some group of neoplastic cells infiltrating the urinary bladder muscle layer. This feature, suggesting a possible protective role of POSTN secreted by CAFs with the aim of containing the neoplastic infiltration, was also noted in a recent study on human urothelial carcinomas, even if the research was focused on the tumor affecting the upper urinary tract (42).…”

“…Mitotic count, although a negative prognostic factor, is, however, not considered a distinguishing criterion for histological grading, so there are no cutoffs for mitotic count in veterinary medicine any more than there are for human medicine (30). In a recent study on human urothelial carcinoma of the urinary tract, the statistical relationships with periostin expression and epidemiological and histological features have been investigated, revealing that there was no significant difference in the mean age, sex, tumor laterality, or histological grade between patients with low and high stromal periostin expression, while the frequencies of tumors with nonpapillary gross findings were significantly higher in patients with high stromal periostin expression than in those with low expression (42). The latter correlation between increased periostin expression and papillary tumor morphology is not confirmed by the present study.…”

Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma

“…Immunohistochemical staining images were observed under a microscope and several fields were randomly selected for observation at high magnification. The immunohistochemical staining results were interpreted using a commonly used semi-quantitative scoring method 21 ( Table 1 ).…”

IL-6 induces periostin production in human ACL remnants: a possible mechanism causing post-traumatic osteoarthritis

“…Periostin (POSTN), a secreted extracellular protein, has many biological functions and plays key roles in various diseases [ 14 ]. The deregulation of POSTN occurs in cancers [ 15 – 17 ], cardiovascular diseases [ 18 , 19 ], and respiratory disorders [ 20 , 21 ]. Recent evidence has shown that it is also upregulated in osteoarthritis (OA) [ 22 – 27 ].…”