Recurrence-free and overall survival according to EGFR, HER2 and HER3 expression in I-type adenocarcinoma.

<p>Kaplan Meier analysis of five-year recurrence-free survival in strata according to high and low expression of (A) EGFR, (C) HER2, (E) HER3 and overall survival according to high and low expression of (B) EGFR, (D) HER2, and (F) HER3.</p

Prognostic effect of hENT1, dCK and HuR expression by morphological type in periampullary adenocarcinoma, including pancreatic cancer

<p><i>Background</i>: Putative biomarkers of gemcitabine response have been extensively studied in pancreatic cancer, but less so in other types of periampullary adenocarcinoma. The most studied biomarker is human equilibrative nucleoside transporter 1 (hENT1), and the activating enzyme deoxycytidine kinase (dCK) has also been linked to treatment response. The RNA-binding protein human antigen R (HuR) has been demonstrated to confer increased dCK levels in vitro and to predict gemcitabine response in vivo. Here, we investigated the prognostic impact of hENT1, dCK and HuR in pancreatobiliary (PB) and intestinal (I) type periampullary cancers, respectively. <i>Material and methods</i>: Immunohistochemical expression of hENT1, dCK and HuR was evaluated in tissue microarrays with all primary tumours and 103 paired lymph node metastases from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinomas. <i>Results</i>: In patients with PB-type tumours, neither hENT1 nor dCK expression was prognostic. A high HuR cytoplasmic/nuclear ratio was associated with a significantly reduced five-year overall survival (OS) in patients receiving adjuvant gemcitabine (HR 2.07, 95% CI 1.03–4.17) but not in untreated patients (p_interaction = 0.028). In patients with I-type tumours receiving adjuvant chemotherapy, high dCK expression was significantly associated with a prolonged recurrence-free survival (RFS) (HR 0.09, 95% CI 0.01–0.73, p_interaction = 0.023). Furthermore, HuR expression was associated with a prolonged OS and RFS in unadjusted but not in adjusted analysis and hENT1 expression was an independent predictor of a prolonged RFS (HR 0.24, 95% CI 0.10–0.59), regardless of adjuvant treatment. <i>Conclusion</i>: hENT1 expression is a favourable prognostic factor in I-type, but not in PB-type tumours. High dCK expression is a favourable prognostic factor in patients with I-type tumours receiving adjuvant treatment and a high cytoplasmic/nuclear HuR ratio is a negative prognostic factor in gemcitabine-treated PB-type tumours. Morphological subtype should always be considered in biomarker studies on periampullary cancer.</p

Cox proportional hazards analysis of the impact of EGFR, HER2 and HER3 expression on recurrence-free and overall survival in patients with I-type adenocarcinoma.

<p>Cox proportional hazards analysis of the impact of EGFR, HER2 and HER3 expression on recurrence-free and overall survival in patients with I-type adenocarcinoma.</p

Sample immunohistochemical images.

<p>Photomicrographs representing different categories of immunohistochemical staining for EGFR, HER2 and HER3, respectively. An image visualizing <i>HER2</i> gene amplification by silver in situ hybridization is shown together with the HER2 3+ case.</p

Expression of EGFR, HER2 and HER3, and amplification status for <i>HER2</i> in pancreatobiliary and intestinal type periampullary adenocarcinoma.

<p>Expression of EGFR, HER2 and HER3, and amplification status for <i>HER2</i> in pancreatobiliary and intestinal type periampullary adenocarcinoma.</p

Recurrence-free and overall survival in strata according to EGFR expression and adjuvant gemcitabine in PB-type adenocarcinoma.

<p>Kaplan Meier analysis of (A) five-year recurrence-free survival and (B) overall survival in combined strata according to EGFR expression (high/low) and adjuvant gemcitabine (yes/no).</p

Cox proportional hazards analysis of the impact of EGFR expression on recurrence-free and overall survival in strata according to adjuvant gemcitabine in patients with PB-type adenocarcinoma.

<p>Cox proportional hazards analysis of the impact of EGFR expression on recurrence-free and overall survival in strata according to adjuvant gemcitabine in patients with PB-type adenocarcinoma.</p

Recurrence-free and overall survival according to EGFR and HER3 expression in PB-type adenocarcinoma.

<p>Kaplan Meier analysis of five-year recurrence-free survival in strata according to high and low expression of (A) EGFR and (C) HER3 and overall survival according to high and low expression of (B) EGFR and (D) HER3.</p

MOESM1 of Relationship between mismatch repair immunophenotype and long-term survival in patients with resected periampullary adenocarcinoma

Additional file 1. Unadjusted and adjusted hazard ratios of the impact of MMR immunophenotype on recurrence free survival in I-type tumors, PB-type tumors, and the entire cohort

საქართველოს საბჭოთა სოციალისტური რესპუბლიკის მთავრობის დადგენილებათა კრებული N3

Additional file 1. Associations between CD1a+ DC-cell infiltration and clinicopathological factors