Histologic categorization of fibrotic cancer stroma in the primary tumor is an independent prognostic index in resectable colorectal liver metastasis.
Although the molecular mechanism of desmoplastic reaction (DR) for providing aggressive tumor characteristics is increasingly recognized, the prognostic role of DR has not been investigated in colorectal liver metastasis (CRLM). A pathologic review of 412 patients who underwent hepatectomy for CRLM at 2 independent institutions was conducted. DR in primary tumors was classified as mature, intermediate, or immature on the basis of the existence of keloid-like collagen and myxoid stroma-distinctive histologic products of extracellular matrix remodeling. With respect to DR, 137, 122, and 153 patients were classified as mature, intermediate, and immature, respectively. Immature DRs were associated with higher T and N stages, higher primary tumor grade, synchronous and larger size of liver metastasis, and extrahepatic disease (P≤0.0001 to 0.002). DR significantly influenced the rate of recurrence in extrahepatic sites, including the lung, peritoneum, and local region in the primary tumor (P≤0.0001 to 0.03), rather than the remnant liver. Five-year overall survival rates after hepatectomy were the highest in the mature group (58.9%), followed by intermediate (42.1%) and immature (26.7%) groups. A significant prognostic impact of DR was observed in subset analyses for institutions, primary tumor location, and timing and number of liver metastases. Multivariate analysis revealed that DR was an independent prognostic factor along with T stage of the primary tumor, size of liver metastasis, and extrahepatic disease. Characterizing DR in the primary tumor on the basis of histologic products of cancer-associated fibroblasts is valuable in evaluating prognostic outcome after hepatectomy in CRLM patients.
Departments of *Surgery §Laboratory Medicine, National Defense Medical College, Saitama †Department of Gastroenterological Surgery ‡Division of Pathology, Cancer Institute Hospital, Tokyo, Japan.
Hideki
H
Ueno
Tsuyoshi
T
Konishi
Yuichi
Y
Ishikawa
Hideyuki
H
Shimazaki
Masashi
M
Ueno
Suefumi
S
Aosasa
Akio
A
Saiura
Kazuo
K
Hase
Junji
J
Yamamoto
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005355:Fibrosis; D006498:Hepatectomy; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000145:classification / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D017154:Stromal Cells / Q000145:classification / Q000473:pathology*; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden