Treatment and histopathological prognostic factors of colorectal cancer pulmonary metastases

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Oulu University Hospital, auditorium 1, Kajaanintie 50

Topic of the dissertation

Treatment and histopathological prognostic factors of colorectal cancer pulmonary metastases

Doctoral candidate

Licenciate of Medcine Topias Karjula

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, Translational Medicine Research Unit

Subject of study



Docent Ilkka Ilonen, University of Helsinki


Docent Olli Helminen, University of Oulu

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Treatment and histopathological prognostic factors in colorectal cancer pulmonary metastases

Lungs are the most common site of metastasis and colorectal cancer (CRC) is one of the most common sources of pulmonary metastases. The treatment and prognostic evaluation of CRC is mainly based on tumor-node-metastasis -classification, but it can also be categorized based on morphology, genetics and also on the host immune response. The prognostic value of several known independent prognostic factors within the primary tumors, are less clear in the metastases.

This doctoral thesis was based on two cohorts. The postoperative trends and results were analyzed in the first cohort including all intended pulmonary metastasectomies performed in Oulu University Hospital (OYS) during 2000–2020. The second cohort included patients treated with pulmonary metastasectomy for CRC in OYS and Central-Finland Central Hospital during 2000–2020. The prognostic value of morphological characteristics such as tumor budding, tumor-stroma ratio (TSR) and host's immune response was analysed from the resected pulmonary metastases. The immune response was evaluated by analyzing T-cell and macrophage densities, and the clustering of immune cells into tertiary lymphoid structures.

According to the results, a significant proportion of the intended pulmonary metastasectomies turn out as incidental primary lung cancers. In the resected CRC pulmonary metastases, tumor budding and TSR had no prognostic value. T-cell infiltration was higher in the pulmonary metastases compared to the primary tumors and had independent prognostic value in the metastases. Tertiary lymphoid structures in the metastases had no survival effect. Tumor-associated macrophages had a more pro-tumoral M2-polarized phenotype in the metastases compared to the primary tumors, and higher densities of M2-like macrophages were associated with worse survival.

The present studies demonstrate the differences between resected CRC metastases and corresponding primary tumors and elucidates the significant prognostic role of the immune system in the metastases. The results of this doctoral thesis might have clinical implications in future therapy planning.
Last updated: 29.4.2024