Image analysis-derived metrics of histomorphological complexity predicts prognosis and treatment response in stage II-III colon cancer.
The complexity of tumor histomorphology reflects underlying tumor biology impacting on natural course and response to treatment. This study presents a method of computer-aided analysis of tissue sections, relying on multifractal (MF) analyses, of cytokeratin-stained tumor sections which quantitatively evaluates of the morphological complexity of the tumor-stroma interface. This approach was applied to colon cancer collection, from an adjuvant treatment randomized study. Metrics obtained with the method acted as independent markers for natural course of the disease, and for benefit of adjuvant treatment. Comparative analyses demonstrated that MF metrics out-performed standard histomorphological features such as tumor grade, budding and configuration of invasive front. Notably, the MF analyses-derived "αmax" -metric constitutes the first response-predictive biomarker in stage II-III colon cancer showing significant interactions with treatment in analyses using a randomized trial-derived study population. Based on these results the method appears as an attractive and easy-to-implement tool for biomarker identification.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.|Department of Pathology, Belarusian State Medical University, Minsk, Belarus.
Artur
A
Mezheyeuski
City Clinical Pathologoanatomic Bureau, Minsk, Belarus.
Ina
I
Hrynchyk
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Mia
M
Karlberg
Department of Pathology, Belarusian State Medical University, Minsk, Belarus.
Anna
A
Portyanko
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Lars
L
Egevad
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Peter
P
Ragnhammar
Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Stockholm, Sweden.
David
D
Edler
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Bengt
B
Glimelius
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Arne
A
Östman
D000368:Aged; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007633:Keratins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis
D007633:Keratins