Collagen patterns in breast cancer
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Background: Research on breast cancer has largely been dominated by research on the epithelial component of the tumour. However, recent studies have shed light on the role the stroma plays in both the development and progression of breast carcinomas. Using multiphoton microscopy(MPM), we investigated some of the structural changes the stroma undergoes in breast cancer. Methods: Whole sections of 8 low grade Luminal A-subtype ductal carcinomas, and 8 high grade HER2-subtype ductal carcinomas were examined using second harmonic generation microscopy. Two 3D-images were made of each of the following zones in each case: intratumoral zone, juxtatumoral zone, and extratumoral zone. Differences in collagenstructure were examined in the three zones in each case, in addition to differences between high grade and low grade tumours. The images were evaluated digitally measuring two types of angles: the intrafibrillar angle as an expression of how straight or curly the individual fibres were, and an interfibrillar angle as an expression of the variance in fibre direction. The collagen patterns were also classified by two independent observers as curly, straight or intermediate, based on a blinded assessment of the images. Results: Collagen fibres were straightest in the intratumoral zone, and most curly in the extratumoral zone. Fibres in the juxtatumoral zone were less curly than those in the extratumoral zone, but curlier than those in the intratumoral zone. Collagen fibres in the juxtatumoral zone ran more parallel to each other than in the other zones. Collagen fibres in the juxtatumoral zone tend to run more parallel in high malignant than low malignant tumours (p=0.065). Conclusion: In the process of carcinogenesis, the breast stroma is reorganized with collagen fibres at the tumour-stroma boundary straightening and becoming oriented in such a way that they radiate out from the tumour. This weakening of the normal barrier that the stroma comprises, may promote invasion.