Prediction of distant metastases after curative surgery for rectal cancer.
BACKGROUND
This study was performed to define selection criteria for adjuvant therapy in rectal cancer.


METHODS
An immunohistochemical analysis using nine monoclonal antibodies against CEA, CD15s, CD44v6, DCC, E-cadherin, EGF-R, NM23, PAI-1, and P53 was performed on paraffin sections of two matched (age, gender, UICC stage [I-III], year of operation [1982-1991]) groups of patients (n = 2 x 64) with rectal carcinoma curatively treated by surgery alone. The two groups differed only with regard to metachronous distant metastatic spread. In order to exclude the influence of surgery, all patients had to meet the selection criterion "free of locoregional disease." Follow-up was prospective (median 80 months). Conventional staining procedures and immunohistochemical evaluation were used. Tumor grading and lymphatic and extramural venous invasion were also investigated. Analysis was performed with Fisher's exact test and Kaplan-Meier estimates of disease-free survival (log rank). The Cox model was used for multivariate analysis.


RESULTS
In univariate analysis only grading (P < 0.001) and extramural venous invasion (P < 0.001) correlated significantly with metachronous metastases. In multivariate analysis, beside grading (P = 0.010) and extramural venous invasion (P = 0.011), CD15s (P = 0.042) was also of significance. All other immunohistochemical markers failed.


CONCLUSIONS
The histopathological parameters grading and extramural venous invasion appear to be acceptable predictors of metachronous distant spread in curatively resected rectal cancer. In contrast to the immunohistochemical markers, grading seems to better reflect the individual tumor phenotype and its behavior.
Günther
Klaus
K
Department of Surgery, Biometry and Epidemiology of the University of Erlangen, Erlangen, D-91054 Germany.
Dworak
Otto
O
Remke
Stefan
S
Pflüger
Rafael
R
Merkel
Susanne
S
Hohenberger
Werner
W
Reymond
Marc A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001109:Archives; D015820:Cadherins / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis; D000075389:DCC Receptor; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D007150:Immunohistochemistry; D016256:Lewis X Antigen / Q000032:analysis; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000032:analysis; D015999:Multivariate Analysis; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011956:Receptors, Cell Surface; D012004:Rectal Neoplasms / Q000401:mortality / Q000556:secondary / Q000601:surgery; D013194:Staining and Labeling; D014157:Transcription Factors / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis; D014680:Veins / Q000473:pathology
C112697:CD44v6 antigen; D015820:Cadherins; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D016256:Lewis X Antigen; D054778:NM23 Nucleoside Diphosphate Kinases; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D066246:ErbB Receptors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins