A predictive value of carcinoembryonic antigen in draining venous blood for colorectal cancer patients with postoperative hematogenous metastases.
Tabuchi Y. Nakamura T. Kuniyasu T.
Faculty of Health Science, Kobe University School of Medicine, Japan.
Correlations between carcinoembryonic antigen (CEA) levels of peripheral (p) and draining (d) venous blood and postoperative hematogenous metastases (HM) were examined in 76 advanced (T2-4) colorectal adenocarcinoma patients, to clarify a predictive value of dCEA and the gradient (d-pCEA) between d- and pCEA levels in patients with HM. HM were found in 19 patients (HM group), but not found in 57 patients (non-HM group). The mean value (27.4 ng/ml) of dCEA and positive rates (100 and 89.5%) of d- and d-pCEA levels were significantly higher than those (9.8 ng/ml and 57.9%) of pCEA in the HM group, though no significant difference was found among p-, d-, and d-pCEA values and positive rates in the non-HM group. Significant linear correlations, Y (log dCEA, ng/ml) = -0.039X (month) + 2.016 and Y (log d-pCEA, ng/ml) = -0.039X (month) + 1.823, were found between d- and d-pCEA levels and HM-diagnostic period. These results suggest that colorectal cancer patients with HM are more effectively predicted by the determination of d- and d-pCEA levels than of pCEA levels and that they are patients with positive d- and d-pCEA levels. These patients seem to have a high possibility of early HM.
Epidermal growth factor-related peptides as targets for experimental therapy of human colon carcinoma.
Normanno N. De Luca A. Salomon DS. Ciardiello F.
Oncologia Sperimentale D, ITN-Fondazione Pascale, Naples, Italy.
Colorectal carcinomas generally show a poor sensitivity to conventional chemotherapeutics. Therefore, novel therapeutic approaches are required to improve the prognosis of colon cancer patients in advanced stage. Several growth factors are involved in the control of colon carcinoma cell proliferation. In particular, the epidermal growth factor (EGF)-related peptides transforming growth factor-alpha (TGF-alpha), amphi-regulin (AR), and CRIPTO (CR) are frequently overexpressed in human colon carcinomas. It has also been recently demonstrated that they can function as autocrine growth factors in human colon carcinoma cells. In fact, antisense (AS) retroviral expression vectors or AS oligonucleotides directed against TGF-alpha, AR, or CR are able to inhibit growth and transformation of several human colon carcinoma cell lines. These data suggest that the EGF-like growth factors and their receptors offer potential as targets for experimental therapy of human colon carcinoma. This article reviews the most recent findings in this field.
Evaluation of cell-mediated immunity and circulating immune complexes as prognostic indicators in cancer patients.
Aziz M. Akhtar S. Malik A.
Department of Pathology, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, India.
Cell-mediated immunity (CMI) and circulating immune complexes (CIC) were estimated in 55 cancer patients and 25 control volunteers to evaluate their prognostic significance. Cancer patients comprised head and neck cancer (11), breast cancer (13), gastrointestinal cancer (10), genitourinary cancer (11), and lymphomas and sarcomas (10). CMI was tested in vitro by early rosette-forming cells (ARFC) and total rosette-forming cell (TRFC) counts. ARFC count in control group was 758.1 +/- 78.09 cells/cumm. In advancing clinical stages of cancer (I-IV), ARFC counts were decreased (i.e., 601.12 +/- 74.96 [p < 0.01]; 494.8 +/- 71.83 [p < 0.001]; 432.44 +/- 36.05 [p < 0.001], and 438.55 +/- 69.99 [p < 0.001] cells/cumm, respectively). TRFC count in control group was 1029 +/- 88.39 cells/cumm. In cancer stages I through IV, these counts decreased significantly (i.e., 699.63 +/- 66.24; 597.55 +/- 82.9; 505.11 +/- 52.56; and 501.55 +/- 69.99 cells/cumm, respectively [p < 0.001]. Dinitrochlorobenzene cutaneous reactivity in vivo was 100% positive in control group, 62.5% positive in cancer stage I, 5% positive in stage II, and negative in stages III and IV. CIC of intermediate size were estimated by polyethylene glycol precipitation (PEG pptn) technique, which detects CIC in the ratio of 2:1 (Ag2Ab). Mean PEG index in control group was 39.5 +/- 4.65; sequential increase in CIC was observed in advancing clinical stages of cancer (I-IV)(i.e., 49 +/- 7.03 [p < 0.01]; 75.38 +/- 44.01 [p < 0.001]; 93.38 +/- 44.57 [p < 0.001]; and 216.00 +/- 147.05 [p < 0.001], respectively). Latex agglutination inhibition (LAI) titer was done to detect CIC as small as 8s, which constitute the opposite polar end of CIC spectrum. LAI titers in control group were nil. However, LAI titers in cancer stages I through IV were 1 +/- 2.64; 8.6 +/- 5.6 (p < 0.001); 12.00 +/- 8.11 (p < 0.001); and 25.77 +/- 9.06 (p < 0.001), respectively. Decrease in CMI and subsequent increase in CIC indicate unfavorable prognosis in cancer patients, and also precede clinical manifestation of increased tumor mass in vivo.
Prognostic significance of c-erbB-2 gene expression in the poorly differentiated type of adenocarcinoma of the stomach.
Yonemura Y. Ninomiya I. Tsugawa K. Fushida S. Fujimura T. Miyazaki I. Uchibayashi T. Endou Y. Sasaki T.
Department of Surgery II, School of Medicine, Kanazawa University, Japan.
Prognostic significance of c-erbB-2 gene abnormalities is unclear in the poorly differentiated type of gastric carcinoma, because the abnormalities of this gene have been reported to be restricted to the differentiated type of gastric carcinoma. In this study, correlation of c-erbB-2 gene amplification/overexpression of mRNA and protein were studied in the poorly differentiated type of gastric carcinoma. c-erbB-2 gene amplification determined by the slot-blot hybridization was observed in 11 (13%) of 82 gastric cancer, and 8 of 11 tumors were poorly differentiated. In addition, c-erbB-2 mRNA expression was studied by the reverse transcriptase-polymerase chain reaction. Four (17%) of 24 tumors showed overexpression of c-erbB-2 mRNA, and all these four exhibited morphologically a poorly differentiated type. Among 157 poorly differentiated gastric cancers, 20 (13%) tumors showed immunohistochemically c-erbB-2 protein expression. These tumors had significantly higher incidences of larger tumor, serosal invasion-positive tumors, node-positive tumor, or peritoneal dissemination-positive tumor than those without c-erbB-2 expression. Furthermore, patients with c-erbB-2 protein overexpression ran poorer prognoses than those without c-erbB-2 expression. From these results, we conclude that expression c-erbB-2 tissue status may be a good prognostic indicator in poorly differentiated gastric carcinoma.
Shared tumor antigens in colorectal carcinoma and neuroendocrine tumors.
Tobi M. Darmon E. Rozen P. Baratz M. Lundqvist M. Oberg K. Thomas P. Esteban J. Hefta S. Paxton R. Shively J.
Department of Gastroenterology and Pathology, Tel Aviv Medical Center, Sackler School of Medicine, Israel.
ND4 monoclonal antibody recognizes a tumor marker found on poorly differentiated colorectal cancer. We demonstrate its expression in 25% of gastrointestinal neuroendocrine tumors, which also express CEA in 37% of cases. As in colorectal cancer the ND4 marker is predominantly membrane bound in a colonic neuroendocrine tumor cell line, LCC-18 (p < 0.05). The ND4 marker is absent in a poorly differentiated colorectal cancer cell line that does not express CEA or other tumor antigens. Shed antigen in the serum of patients with neuroendocrine tumors is detected in only five of seven patients with the carcinoid syndrome and two of four of those without evidence of the syndrome. However, the reactivity was less in the patients with localized disease, and this test is unlikely to be of diagnostic utility in this group of patients. The sharing of this antigen in colorectal cancer and neuroendocrine tumors is not universal, but does support the common-cell progenitor theory for the origin of these tumors.
Aspirin use and p53 expression in colorectal cancer.
Freedman AN. Michalek AM. Weiss HA. Zhang ZF. Marshall JR. Mettlin CJ. Asirwatham JE. Petrelli NJ. Caporaso NE.
Genetic Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
p53 protein overexpression indicates loss of tumor suppressor activity and is the most common genetic alteration in colorectal neoplasms. Epidemiologic and experimental studies suggest that regular use of aspirin may reduce colorectal cancer risk. We set out to determine whether p53 overexpression of the colorectum was associated with a patient's history of aspirin use. Self-administered questionnaires, including information on aspirin use, were obtained from 163 patients with nonfamilial colorectal cancer and from 326 healthy controls. Nuclear p53 protein overexpression using anti-p53 CM-1 polyclonal antibody was observed in 44.8% (73/163) of patients' tumors. A nonsignificant inverse association was observed between use of aspirin and colorectal cancer. Compared with that for nonusers, the odds ratio (OR) for individuals who took aspirin at least twice weekly was 0.68 (95% confidence interval [95% CI]: 0.39-1.18). The odds ratio for those individuals who used aspirin for less than 5 years was 0.54 (95% CI: 0.24-1.23), and 0.80 (95% CI: 0.42-1.51) for those who used aspirin for 5 years or more, when compared with nonusers. An inverse association of regular aspirin use (two times per week or more) was found both for cases with p53 overexpression (OR: 0.79; 95% CI: 0.39-1.59), and for cases without p53 overexpression (OR: 0.56; 95% CI: 0.25-1.22). There was little evidence of a difference in the effect of aspirin use on cancer risk between cases with and without p53 overexpression, even after adjustment for potential confounders.
Relations of nm23 expression to clinicopathologic variables and proliferative activity of gastric cancer lesions.
Nakamura T. Tabuchi Y. Ohno M.
First Department of Surgery, Kobe University School of Medicine, Japan.
Relationships of nm23 expression and 12 clinicopathologic variables and proliferative activity of cancer cells were examined in 55 gastric cancer patients to clarify the effects of nm23 expression on the factors and activity in gastric cancer. Expression of nm23 was determined by immunohistochemically stained sections using a monoclonal antibody, nm23H-1. Proliferative activity was immunohistochemically evaluated by proliferating cell nuclear antigen (PCNA) labeling index (LI) using a monoclonal antibody PC10. Expression of nm23 was found in 24 lesions (positive group) but not in 31 lesions (negative group). With regard to clinicopathologic variables, a significant (p < 0.05) difference between the positive and negative groups was found in 1 of the 12 factors, depth of cancer invasion. PCNA LI (48.9 +/- 11.6%) of the former group was significantly (p < 0.05) higher than that (40.3 +/- 12.6%) ot the latter, although multiple regression analysis showed that nm23 expression was not one of the most influencing variables for PCNA LI. The results may suggest that expression of nm23 in gastric cancer lesions is correlated to tumor progression and/or proliferation rather than suppression of metastasis.