Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect--a histopathological and immunohistochemical study.
BACKGROUND
Invasion and metastasis is a complex process governed by the interaction of genetically altered tumor cells and the immunological and inflammatory host response. Specific T-cells directed against tumor cells and the nonspecific inflammatory reaction due to tissue damage, cooperate against invasive tumor cells in order to prevent recurrences. Data concerning involvement of individual cell types are readily available but little is known about the coordinate interactions between both forms of immune response.


METHODS
The presence of inflammatory infiltrate and eosinophils was determined in 1530 patients with rectal adenocarcinoma from a multicenter trial. We selected 160 patients to analyze this inflammatory infiltrate in more detail using immunohistochemistry. The association with the development of local and distant relapses was determined using univariate and multivariate log rank testing.


RESULTS
Patients with an extensive inflammatory infiltrate around the tumor had lower recurrence rates (3.4% versus 6.9%, p = 0.03), showing the importance of host response against tumor cells. In particular, peritumoral mast cells prevent local and distant recurrence (44% versus 15%, p = 0.007 and 86% versus 21%, p < 0.0001, respectively), with improved survival as a consequence. The presence of intratumoral T-cells had independent prognostic value for the occurrence of distant metastases (32% versus 76%, p < 0.0001).


CONCLUSIONS
We showed that next to properties of tumor cells, the amount and type of inflammation is also relevant in the control of rectal cancer. Knowledge of the factors involved may lead to new approaches in the management of rectal cancer.
Nagtegaal
I D
ID
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. I.Nagtegaal@pathol.azn.nl
Marijnen
C A
CA
Kranenbarg
E K
EK
Mulder-Stapel
A
A
Hermans
J
J
van de Velde
C J
CJ
van Krieken
J H
JH
D000230:Adenocarcinoma / Q000737:chemistry / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D017252:CD3 Complex / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002634:Chemotaxis, Leukocyte; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D006098:Granulocytes / Q000276:immunology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000737:chemistry* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012004:Rectal Neoplasms / Q000737:chemistry* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology
D017252:CD3 Complex