title: Platelets surrounding primary tumor cells are related to chemoresistance.
abstract: Platelets are crucial components of the tumor microenvironment that function to promote tumor progression and metastasis. In the circulation, the interaction between tumor cells and platelets increases invasiveness, protects tumor cells from shear stress and immune surveillance, and facilitates tumor cell extravasation to distant sites. However, the role and presence of platelets in the primary tumor have not been fully determined. Here, we investigated the presence of platelets around breast cancer primary tumor cells and the associations between these cells. We further investigated the associations among platelets, tumor cells, chemoresistance, and epithelial-mesenchymal transition (EMT). We retrospectively analyzed data from 74 patients with human epidermal growth factor receptor 2 (HER2)‑negative breast cancer who underwent biopsies before treatment and subsequent neo-adjuvant chemotherapy. In biopsy specimens, we evaluated the expression of platelet-specific markers and EMT markers using immunohistochemistry. The associations among the expression of platelet‑specific markers in biopsy specimens, EMT, response to neo‑adjuvant chemotherapy, and survival were analyzed. The presence of platelets was observed in 44 out of 74 (59%) primary breast cancer biopsy specimens. Platelet‑positive tumor cells showed EMT‑like morphological changes and EMT marker expression. Primary tumor cells associated with platelets were less responsive to neo‑adjuvant chemotherapy (pCR rate: 10 vs. 50%, respectively; p=0.0001). Platelets were an independent predictor of the response to chemotherapy upon multivariable analysis (p<0.0001). In conclusion, there was a significant association between platelets surrounding primary tumor cells in the biopsy specimens and the chemotherapeutic response in breast cancer. Platelets surrounding primary tumor cells may represent novel predictors of chemotherapeutic responses.
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inokuchi
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Oyama
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Tajima
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Takamura
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Itasu
authors.initials: I
authors.lastname: Ninomiya
authors.affiliation: Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: A Karim
authors.initials: AK
authors.lastname: Ahmed
authors.affiliation: Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Harman
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.affiliation: Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001792:Blood Platelets / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human