title: Two progressive pathways of microinvasive carcinoma: low-grade luminal pathway and high-grade HER2 pathway based on high tumour-infiltrating lymphocytes.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Kurume University Medical Center, Kurume, Fukuoka, Japan Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan.
authors.forename: Michi
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Pathology and Laboratory Medicine, Kurume University Medical Center, Kurume, Fukuoka, Japan Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Rin
authors.initials: R
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgery, Japan Community Healthcare Organization Kurume General Hospital, Kurume, Fukuoka, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Tse
authors.affiliation: Department of Surgery, Japan Community Healthcare Organization Kurume General Hospital, Kurume, Fukuoka, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgery, Japan Community Healthcare Organization Kurume General Hospital, Kurume, Fukuoka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Otsuka
authors.affiliation: Department of Pathology, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kanomata
authors.affiliation: Department of Surgery, Nagasaki Harbor Medical Center, Nagasaki, Nagasaki, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Minami
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Eguchi
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yano
mesh_terms: D000328:Adult; D000368:Aged; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007564:Japan; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: BREAST CANCER; HISTOPATHOLOGY; TUMOUR IMMUNITY