The relationship between tumour necrosis, tumour proliferation, local and systemic inflammation, microvessel density and survival in patients undergoing potentially curative resection of oesophageal adenocarcinoma

Abstract

Background:There is increasing evidence that the local and systemic inflammatory responses are associated with survival in oesophageal cancer. The aim of this study was to examine the relationship between tumour necrosis, tumour proliferation, local and systemic inflammation and microvessel density and survival in patients undergoing potentially curative resection of oesophageal adenocarcinoma.Methods:The interrelationship between tumour necrosis, tumour proliferation, local inflammatory response (Klintrup–Makinen criteria, intra-tumoural CD8+ lymphocyte and macrophage infiltration), systemic inflammatory response (modified Glasgow Prognostic score (mGPS)), and microvessel density was examined in 121 patients undergoing potentially curative resection for oesophageal adenocarcinoma (including type I and II tumours of the gastro-oesophageal junction).Results:Tumour necrosis was not significantly associated with any tumour measure other than the degree of differentiation. On multivariate analysis, only age (HR 1.93, 95% CI 1.23–3.04, P=0.004), mGPS (HR 2.91, 95% CI 1.51–5.62, P=0.001), positive to total lymph node ratio (HR 2.38, 95% CI 1.60–3.52, P<0.001) and macrophage infiltration (HR 1.49, 95% CI 1.02–2.18, P=0.041) were independently associated with cancer-specific survival in oesophageal adenocarcinoma. Intra-tumoural macrophages were associated with tumour proliferation (P<0.001) and CD8+ lymphocytes infiltration (P<0.01).Conclusion:The results of this study suggest that tumour necrosis does not link local and systemic inflammatory responses and is not significantly associated with survival. In contrast, tumour macrophage infiltration appears to have a central role in the proliferative activity and the coordination of the inflammatory cell infiltrate and is independently associated with poorer survival in patients with oesophageal adenocarcinoma.

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

“…2). In addition, three articles evaluated patients’ CSS [13, 14, 25]. And the pooled results showed CD8 + TILs were not associated with patients’ CSS ( P = 0.268) (Fig.…”

“…A total of 16 articles, including 2121 patients, investigated the prognostic value of CD8 + TILs in patients with EC [11-14, 24, 25, 28, 30-33, 35, 37-40]. Thirteen articles evaluated patients’ OS [11, 12, 24, 28, 30-33, 35, 37-40].…”

DHH is an Independent Prognosticator of Oncologic Outcome of Clear Cell Renal Cell Carcinoma

“…18 For each biomarker the staining pattern (nuclear vs cytoplasmic vs membranous) was evaluated. Representative cores (clearly positive, clearly negative and mixed positive/negative) were manually identified to create color segmentation.…”

Trial watch

“…Thus, no statistically significant association between high levels of CD68 + cells within neoplastic lesions and clinicopathological parameters including disease course has been detected in cohorts of nasopharyngeal carcinoma (n = 119) and endometrial cancer (n = 109) patients 227 , 238 . Tumor infiltration by CD68 + macrophages has been linked to worsened disease course in cohorts of breast carcinoma patients (n = 249), in relationship with increased microvessel density and VEGF expression; 239 HNC patients who underwent surgery for the removal of laryngeal lesions (n = 98); 240 patients subjected to potentially curative resection of esophageal cancers (n = 56 and n = 121); 241 , 242 resected gastric cancer patients (n = 97), 243 subjects with resected HCC (n = 137); 244 lung adenocarcinoma patients (n = 113), again in association with increased local angiogenesis; 245 pleural mesothelioma patients who underwent cytoreductive surgery (n = 52), a setting in which also circulating monocytes correlated with poor survival; 246 melanoma patients (n = 58, n = 202 and n = 190), high macrophage counts being associated with markers of aggressive disease including Breslow thickness, ulceration and mitotic rate; 87 , 247 , 248 subjects affected by ovarian carcinoma (n = 67); 249 bladder cancer patients receiving intravesical instillations of the bacillus Calmette-Guérin (BCG) (n = 41); 250 prostate cancer patients treated with hormonal therapy (n = 71), a setting in which macrophage infiltration was shown to predict resistance to treatment; 251 and patients affected by renal pelvis and ureteral transitional cell carcinomas (n = 75) 252 . Conversely, tumor infiltration by macrophages (most often detected as CD68 + cells) has been correlated with improved disease outcome in cohorts of HNC patients bearing nasopharyngeal lesions (n = 45) 212 or treated with IRX-2-based immunotherapy (n = 27); 67 patients bearing differentiated thyroid carcinoma (n = 398); 45 NSCLC patients who underwent surgical resection (n = 175) 253 or receiving chemotherapy for stage IV lesions (n = 199); 49 gastric cancer patients (n = 84), highlighting a correlation between intratumoral macrophages, intratumoral CD8 + T cells and tumor cell apoptosis; 254 HCC patients who underwent surgical resection (n = 302); 96 melanoma patients treated with oral BCG (n = 25); 255 CRC patients (n = 97, n = 70, n = 446 and n = 160), overall suggesting a critical role of macrophages at the tumor invasive margin; 60 , 256 - 258 and patients affected by various solid tumors (including breast carcinoma, melanoma and RCC) subjected to IL-2-based immunotherapy 77 .…”