Pathologic Response of HER2-positive Gastric Cancer to Trastuzumab-based Chemotherapy.
Trastuzumab-based chemotherapy is now a standard approach for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. However, histopathologic changes after treatment have yet to be elucidated. This study aims to characterize the histologic response of gastric cancer to trastuzumab treatment and its correlation with HER2 status. Twenty-one advanced HER2-positive gastric cancers treated with trastuzumab-based chemotherapy, including 10 surgically resected specimens and 11 biopsy samples from patients with inoperable tumors, were evaluated for the histologic responses and HER2 status of residual cells. We also reviewed, as controls, 10 cases undergoing surgical resection of tumors after chemotherapy without trastuzumab. Complete and partial histologic responses were obtained in 2 and 8 of the surgical cases, respectively. HER2-positive neoplastic cells were recognized at least focally in the 8 cases. Notably, the proportion of HER2-positive cells was always higher in superficial (mucosal/submucosal) layers than in deeper layers. Three specimens contained HER2-positive neoplastic cells exclusively in the superficial area or intravascular space, whereas deeply invasive or metastatic components almost completely disappeared or were HER2 negative when still present. In contrast, HER2-negative cells or residual tumor cells in control cases tended to survive as well or better in deeply invasive areas or in metastases than in superficial areas. Biopsy samples from nonoperative patients remained HER2 positive after treatment in 8 of 11 patients. Our observations suggest that HER2-positive neoplastic cells tend to survive within superficial areas or intravascular spaces after trastuzumab therapy, even when deeply invasive or metastatic lesions responded well to therapy.
Departments of *Gastrointestinal Surgery †Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Masayuki
M
Urabe
Tetsuo
T
Ushiku
Yasuyuki
Y
Seto
Masashi
M
Fukayama
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005260:Female; D005743:Gastrectomy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000068878:Trastuzumab / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human