Reproducibility and validation of tumour stroma ratio scoring on oesophageal adenocarcinoma biopsies
Introduction
Partial oesophagectomy is the mainstay in potentially curative treatment for oesophageal cancer. Postoperative mortality has decreased substantially in recent years, mainly as a result of more precise preoperative staging and better patient selection.1, 2, 3 Still, many patients present with recurrences within two years after surgery and even in specialised high volume centres, 5-year survival rates rarely exceed 40%.4, 5, 6
Histopathological factors, such as extracapsular lymph node involvement and possibly genetic expression profiling of the tumour, are in relation with metastatic potential and survival.7, 8 The tumour micro-environment, including the supportive stromal component, plays a crucial role in the progression, growth and spread of cancers.9, 10, 11 Earlier, we found that the amount of stroma in direct relation to the tumour was an independent prognostic factor for survival in colon cancer12, 13 and breast cancer.14
Subsequently, we have investigated the tumour stroma ratio (TSR) on histological sections of oesophagectomy specimens.15 In a set of 93 patients who underwent resection for oesophageal adenocarcinoma, a significant difference in survival time was observed between patients with a high TSR (⩾50%) and patients with a low TSR (<50%). Patients with a low TSR showed a significantly worse survival. Since neoadjuvant therapies are increasingly used, and patient selection for multimodality treatment becomes even more important, assessment of prognostic factors is preferably done before the start of treatment. Therefore, TSR scoring should be validated on biopsy specimens.
The objectives of the present study were: (1) to assess inter- and intraobserver agreement for TSR scoring on oesophageal adenocarcinoma biopsies, and (2) to correlate these biopsy results with the results derived from the surgical specimens and with survival data.
Section snippets
Tissue selection
From the database of the Comprehensive Cancer Centre Leiden (CCCL), we had previously selected a consecutive series of 93 patients with oesophageal adenocarcinoma who underwent resection with curative intent between 1990 and 2004 at the Leiden University Medical Centre (LUMC) or the Reinier de Graaf Gasthuis in Delft (RdGG).15 Patients who were treated with neoadjuvant therapy were excluded, as were patients who died within 30 d after surgery. Patient, tumour and treatment characteristics were
Patient demographics
Archival biopsy material was available for 91 of the 93 patients who underwent oesophagectomy. Biopsies of 10 (11%) patients were unanimously rejected because of the poor quality of the tissue specimen. The median age of the 81 study patients was 64 (range 37–82) years. There were 66 men (81.5%) and 15 women (18.5%). Median follow-up was 23 (range 3–220) months.
Histopathological features
Overall, there were 486 TSR biopsy scores (81 slides, three observers and two scores per observer for each slide). A definitive TSR
Discussion
Our study results showed that TSR biopsy scoring in patients with oesophageal adenocarcinoma was reproducible. Biopsy results demonstrated moderate correlation with results derived from surgical specimens. The definitive TSR biopsy score was an independent prognostic factor for survival. A high score (TSR ⩾50%) was associated with better survival.
Concordant with our previous study results on surgical resection specimens, scoring of TSR on biopsy material was easy on H&E stained sections.
Conflict of interest statement
None declared.
Sources of support
None.
Financial disclosure
None.
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2021, Biochimica et Biophysica Acta - Reviews on CancerCitation Excerpt :This is thought to be due to the interplay between cancer-associated fibroblasts (CAFs), which make up the tumour stroma and tumour cells and other cell types present in TME, which promote tumourigenesis and metastatic dissemination. Studies examining TSR in both OAC and OSCC support this [39,151]. Therefore, OAC and OSCC patients exhibiting high TSR scores will likely benefit from therapeutics strategies that target multiple critical signalling pathways between tumour and stromal cells.
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2020, European Journal of RadiologyCitation Excerpt :Remarkably, both cohorts had an almost 50/50 distribution between the TSR categories, which is an uncommon observation since previous colorectal studies typically report a 30/70 ratio for stroma-high and stroma-low tumours, respectively [7,9,10,13,41–43]. However, if a sampling bias would have occurred, an underestimation of the stroma-high tumours would have been more sensible, which was apparent in two studies performed in colon- and oesophageal cancer [44,45]. In these studies, the TSR was determined in diagnostic biopsies and demonstrated the expected lower amount of stroma-high tumours.