Multiplexed analysis of macrophage polarisation in pulmonary metastases of microsatellite stable colorectal cancer

Tumour-associated macrophages (TAMs) express a continuum of phenotypes ranging from an anti-tumoural M1-like phenotype to a pro-tumoural M2-like phenotype. During cancer progression, TAMs may shift to a more M2-like polarisation state, but the role of TAMs in CRC metastases is unclear. We conducted a comprehensive spatial and prognostic analysis of TAMs in CRC pulmonary metastases and corresponding primary tumours using multiplexed immunohistochemistry and machine learning-based image analysis. We obtained data from 106 resected pulmonary metastases and 74 corresponding primary tumours. TAMs in the resected pulmonary metastases were located closer to the cancer cells and presented a more M2-like polarised state in comparison to the primary tumours. Higher stromal M2-like macrophage densities in the invasive margin of pulmonary metastases were associated with worse 5-year overall survival (HR 3.19, 95% CI 1.35–7.55, p = 0.008). The results of this study highlight the value of multiplexed analysis of macrophage polarisation in cancer metastases and might have clinical implications in future cancer therapy.Peer reviewe

Results of intention-to-treat pulmonary metastasectomies in northern Finland revealing significant number of new lung primary carcinomas:time to move on from wedge resections?

Abstract Background: A considerable proportion of intended pulmonary metastasectomies is known to turn out as new incidental primary lung cancers in final pathology. We aimed to analyse the trends and results of pulmonary metastasectomies using the intention-to-treat approach with an emphasis on final histopathological findings. Methods: All intention-to-treat pulmonary metastasectomies performed in Oulu University Hospital between 2000 and 2020 were included in the study. Long term survival was analysed with the Kaplan-Meier method and log-rank tests. A binary logistic regression analysis was performed to calculate odds ratios for incidental primary lung cancer in final histology. Results: A total of 154 intended pulmonary metastasectomies were performed to 127 individual patients. There was an increasing trend in pulmonary metastasectomies during the study period. Despite the increasing trend in comorbidities of the operated patients, the length of hospital stays decreased, and the postoperative complication rates remained stable. In final pathology reports, 9.7% were new primary lung cancers and 13.0% were benign nodules. A long disease-free interval (≥24 months) and smoking history were associated with incidental primary lung cancer in final histology. The short-term 30- and 90-day mortalities after pulmonary metastasectomy were 0.7%. The 5-year survival after pulmonary metastasectomy from all histologies was 52.8%, and from colorectal cancer metastasectomies (n=34) it was 73.5%. Conclusions: The significant amount of new primary lung cancer lesions in pulmonary metastasectomy specimens highlight the diagnostic importance of pulmonary metastasectomy. A segmentectomy could be considered as a primary procedure in pulmonary metastasectomy in patients with a long disease-free interval and a heavy smoking history

Tertiary lymphoid structures in pulmonary metastases of microsatellite stable colorectal cancer

Abstract Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates located at sites of chronic inflammation and recognized as prognosticators in several cancers. We aimed to analyse the prognostic effect of TLSs in colorectal cancer (CRC) pulmonary metastases and primary tumours, with a comparison to the CD3+ and CD8+ cell density-based immune cell score (ICS). For TLS density and TLS maximum diameter analysis, 67 pulmonary metastases and 63 primary tumours were stained with haematoxylin and eosin. For ICS scoring and analysis, CD3 and CD8 immunohistochemistry was performed. Excellent interobserver agreement was achieved in all TLS measurements. Of all patients, 36 patients had low TLS density (< 0.222 follicles/mm) and 31 patients had high TLS density (≥ 0.222 follicles/mm) in the first resected pulmonary metastases. TLS density (adjusted HR 0.91, 0.48–1.73) or maximum diameter (adjusted HR 0.78, 0.40–1.51) did not have prognostic value in pulmonary metastases. In primary tumours, higher TLS density (adjusted HR 0.39, 0.18–0.87) and maximum diameter (adjusted HR 0.28, 0.11–0.73) were associated with lower mortality. In the pulmonary metastases, ICS had superior prognostic value to TLSs; however, TLSs and ICS were significantly associated. In conclusion, TLSs in CRC pulmonary metastases had no prognostic value but correlated with the ICS. TLSs in primary tumours associated with favourable prognosis

The prognostic role of tumor budding and tumor-stroma ratio in pulmonary metastasis of colorectal carcinoma

Abstract Objective: To evaluate the prognostic value of tumor budding and tumor-stroma ratio (TSR) in resected pulmonary metastases of colorectal carcinoma (CRC). Methods: In total, 106 pulmonary metastasectomies were performed to 74 patients in two study hospitals during 2000–2020. All relevant clinical data were retrospectively collected. Tumor budding based on the International Tumor Budding Consensus Conference recommendations and TSR in the first resected pulmonary metastases and primary tumors were evaluated from diagnostic hematoxylin-eosin-stained histopathological slides. Results: 60 patients (85.7%) had low tumor budding (≤5 buds/field) and 10 patients (14.3%) had high tumor budding (>5 buds/field) in their first pulmonary metastases of CRC. 5-year overall survival rates of pulmonary metastasectomy in low and high total tumor budding were 28.3% and 37.3% (p = 0.387), respectively. 19 patients (27.1%) had low TSR and 51 patients (72.9%) had high TSR. The 5-year overall survival rates were 32.9% in low and 28.6% in high TSR of first pulmonary metastases (p = 0.746). Tumor budding and TSR did not provide prognostic value in Cox multivariate analysis. Tumor budding and TSR in resected pulmonary metastases were not associated with those of the primary tumor. Conclusion: Tumor budding and TSR in the resected pulmonary metastases of CRC showed no statistically significant prognostic value, however, additional well-powered confirmatory studies are needed