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Two progressive pathways of microinvasive carcinoma: low-grade luminal pathway and high-grade HER2 pathway based on high tumour-infiltrating lymphocytes
  1. Michi Morita1,2,3,
  2. Rin Yamaguchi1,2,
  3. Maki Tanaka4,
  4. Gary M Tse5,
  5. Miki Yamaguchi4,
  6. Hiroko Otsuka4,
  7. Naoki Kanomata6,
  8. Shigeki Minami7,
  9. Susumu Eguchi3,
  10. Hirohisa Yano2
  1. 1Department of Pathology and Laboratory Medicine, Kurume University Medical Center, Kurume, Fukuoka, Japan
  2. 2Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
  3. 3Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan
  4. 4Department of Surgery, Japan Community Healthcare Organization Kurume General Hospital, Kurume, Fukuoka, Japan
  5. 5Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  6. 6Department of Pathology, Kawasaki Medical School, Kurashiki, Okayama, Japan
  7. 7Department of Surgery, Nagasaki Harbor Medical Center, Nagasaki, Nagasaki, Japan
  1. Correspondence to Michi Morita, Department of Pathology and Laboratory Medicine, Kurume University Medical Center, 155-1, Kokubu, Kurume, Fukuoka 839-0863, Japan; mmorita-ngs{at}


Aims While cancer immunity is involved in tumour progression from the very early stage, no detailed study has been reported on the relationship between ‘early-stage’ breast cancer and tumour-infiltrating lymphocytes (TILs). We focused on microinvasive carcinoma to investigate the relationship between histological tumour factors and immunity in ‘early’ breast cancer.

Methods Of 2593 resected breast carcinomas, 46 microinvasive carcinomas (1.8%) were included. The relationships between tumour characteristics (invasive form, grade, comedo, subtype) and immunological characteristics (TIL, healing) were examined. The invasive form was divided into ‘cluster-like’ (ie, invasive foci consisted of a small number of cancer cells) and ‘non-cluster-like’ (ie, nested and classifiable into particular histological type).

Results Among all cases, 34.8% were grade 1. ER+HER2−, ER+HER2+, ER−HER2+ and ER−HER2− accounted for 58.7%, 8.7%, 28.3% and 4.3%, respectively. Compared with ER+HER2−, ER−HER2+ cases had a significantly stronger association with grade 3 (92.3% vs 0%), comedo (100% vs 55.6%), high TIL (100% vs 29.3%), high CD8+ TIL (92.3% vs 33.3%) and healing (76.9% vs 14.8%) (p<0.001). Compared with ‘non-cluster-like’, ‘cluster-like’ carcinoma showed significantly higher rates of HER2 positivity (69.2% vs 24.2%), high TIL (92.3% vs 42.4%) and high CD8+ TIL (76.9% vs 39.4%) (p<0.01).

Conclusions Our study revealed that microinvasive carcinoma has two progressive pathways; ‘low-grade luminal pathway’ and ‘high-grade HER2 pathway’. HER2-positive cases showed the following unique characteristics: ‘high-grade; comedo, high TIL and CD8+ TIL; healing; cluster-like invasion’. These results suggest that the cluster-like invasion might occur because of tumour immunity that leads to disruption of the duct and formation of microinvasive carcinoma in HER2-positive cases.


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