Predictive and prognostic significance of tumour subtype, SSTR1‐5 and e‐cadherin expression in a well‐defined cohort of patients with acromegaly

Abstract

In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1‐5, dopamine D2 receptor, E‐cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E‐cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E‐cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E‐cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.

Cytokeratin 8/18‐negative somatotroph pituitary neuroendocrine tumours (PitNETs, adenomas) show variable morphological features and do not represent a clinicopathologically distinct entity

“…Lack of LMWK expression may thus limit the clinical relevance of the pathology report. In our previously reported cohort we identified 10 such tumours (9%) that either lacked CK 18 immunoreactivity entirely or showed only rare positive cells 17 . This proportion is higher compared to data from other reports (5.9%, 20 of 336), 12,14,15 and may be due to the arbitrary cut‐off of 10% of immunoreactive cells in our study.…”

“…In the CK‐positive tumour group, nine patients underwent treatment with first‐generation somatostatin analogues prior to surgery. As we have previously demonstrated a significant decrease of Ki67 index in pretreated tumours, 17 we excluded them from the analyses of Ki67 and proliferativity (Trouillas A/B). When the group of CK‐negative tumours was compared with rest of the cohort we observed no difference with respect to biochemical, radiological or pathological features (Table 3).…”

“…In total, 114 tumour samples from 110 patients with symptomatic acromegaly were collected in the form of formalin‐fixed paraffin‐embedded tissue. The patient cohort was identical with the cohort described in detail by the authors in previous articles 16,17 . Radiological data (size, Knosp grade of invasion), laboratory data (plasma levels of GH, prolactin, thyroid‐stimulating hormone (TSH) and levels of insulin‐like growth factor 1 (IGF1) expressed as a multiple of age‐adjusted normal levels) were collected either from the RESET registry or from the databases of the participating institutions.…”

“…Radiological data (size, Knosp grade of invasion), laboratory data (plasma levels of GH, prolactin, thyroid‐stimulating hormone (TSH) and levels of insulin‐like growth factor 1 (IGF1) expressed as a multiple of age‐adjusted normal levels) were collected either from the RESET registry or from the databases of the participating institutions. Information concerning the Trouillas prognostic score, 18 histopathological subclassification of the tumours and immunohistochemical expression of CK 18, somatostatin receptor (SSTR) 1, SSTR2A, SSTR3, SSTR5 and D2DR in the form of H‐score have been published previously for the cohort; 17 the same data set was used for the purpose of this article.…”

“…These tumours showed a larger size, lower levels of GH and a greater tendency for prolactin co‐expression in one study, 12 while other studies have not discussed these in more detail. As the lack of identifiable CK pattern significantly impairs the prognostic and predictive value of the histopathological report, we decided to more clearly characterise the clinicopathological features of 10 CK 18‐negative tumours from the cohort of patients that we have described previously 16,17 …”