HER-2/neu overexpression is an independent prognostic factor in colorectal cancer

Background and aims The HER-2/neu protein is intimately involved with normal cell proliferation and tissue growth, as it is extensively homologous and is related to the epidermal growth factor receptor. This phenomenon has been most intensively studied in the context of breast carcinoma, in which its amplification and overexpression correlate with the overall course of disease and poor prognoses, and also constitute a predictive factor of poor response to chemotherapy and endocrine therapy. In this study, we investigated the relationships between the expression of HER-2/neu and the clinicopathological characteristics of colorectal cancer, including survival. This study was performed with a view toward the future introduction of Herceptin therapy for colorectal cancer patients. Patients and methods HER-2/neu overexpression and gene amplification were examined via semiquantitative standardized immunohistochemical staining and fluorescence in situ hybridization (FISH) in 137 colorectal cancer patients who underwent curative surgery at the Kangbuk Samsung Hospital. Results Sixty-five (47.4%) out of 137 patients were determined by immunohistochemistry to have overexpressed HER-2/neu protein. HER-2/neu gene amplification was detected in two patients by FISH. Tumors with HER-2/neu overexpression showed higher postoperative recurrence rate (39.3% vs 14.6%, p=0.013). Tumors with HER-2/neu overexpression were associated with poor 3-year (70.8% vs 83.7%) and 5-year survival rates (55.1% vs 78.3%, p<0.05). Advanced TNM stage, postoperative recurrence, and overexpression of HER-2/neu were found to be independently related to survival by multivariate analysis. Conclusion HER-2/neu overexpression may constitute an independent prognostic factor in colorectal cancer patients, and patients exhibiting HER-2/neu overexpression might constitute potential candidates for a new adjuvant therapy which involves the use of humanized monoclonal antibodies.     

Clinical significance of the quantitative assessment of the cytosolic concentration of HER-2/neu protein in breast cancer by immunoenzymatic assay (ELISA)

Purpose: Retrospective analysis to assess the prognostic and predictive value of HER-2/ neu expression in breast tumors, quantified by enzyme immunoassay (ELISA).Methods: Quantification of HER-2/neu was performed on cytosolic extracts from 914 cases of primary invasive breast carcinomas. Relapse-free and overall survival data were available from 889 patients. The prognostic value of HER-2/neu levels was assessed considering them as a continuous, dichotomic or quartile variable.Results: Cytosolic HER-2/neu levels ranged widely in breast carcinomas (median: 746.5 NHU/mg; range: 2.8–80,000 NHU/mg protein). HER-2/neu protein levels were significantly higher in either moderately or poorly differentiated tumors, as well as in those showing a ductal histological type, aneuploidy or a high S-phase fraction. There was a significant and positive association between cytosolic and membranous HER-2/neu levels (n=162, r sub S=0.53; P<0.0001). In addition, cytosolic HER-2/neu level correlated weakly with progesterone receptors but not with estrogen receptors. Elevated cytosolic HER-2/neu levels (≥1,400 NHU/mg protein) were associated with a high probability of both shortened relapse-free survival and overall survival. This same cut-off value was obtained when we divided the overall group of patients in a training set. However, this HER-2/neu value did not achieve any statistical significance in a validation set used to make sure that the cut-off was correct. Nevertheless, when we divided the obtained data into three different groups with respect to the quartile values (Q) of the intratumoral oncoprotein levels (≤ Q ₁ vs Q ₁−Q ₂ vs > Q ₃), we observed that patients with either low HER-2/ neu levels (≤ Q ₁) or high HER-2/neu levels (> Q ₃) had shorter both relapse-free survival and overall survival curves than those patients with intermediate HER-2/neu levels. On the other hand, high HER-2/neu levels predicted a poor response to adjuvant chemotherapy but not to adjuvant hormonal therapy with tamoxifen.Conclusions: The results of the present investigation indicate that by quantitatively determining the content of HER-2/neu oncoprotein, groups of high-risk breast cancer patients could be identified, for a more effective clinical management.     

HER-2/<Emphasis Type="Italic">neu</Emphasis> status and response to CMF: retrospective study in a series of operable breast cancer treated with primary CMF chemotherapy

Purpose Primary chemotherapy brings the opportunity for an early and accurate assessment of response and offers an ideal model to search for new predictors of response. HER-2/neu is one of the most studied genes for this purpose. Patients and methods Her-2/neu was tested in a non-randomized series of 300 patients with operable breast carcinomas treated with primary CMF. Response was assessed by mammography. Disease-free survival (DFS) and overall survival (OS) were calculated after a mean follow-up of 116 months. Statistical analysis was performed to study the association between HER-2/neu status and response to CMF. Results Overexpression/amplification was found in 23.66% cases. Univariate analysis showed that response was similar in HER-2/neu positive and negative tumors (51.38 vs. 47.36%, P = 0.6). Triple negative tumors (ER, PR and HER-2/neu negative) presented the highest response rate (64.9%). By multivariate analysis, response was significantly correlated to higher nuclear grade and negative estrogen receptor status (P = 0.02 and 0.007, respectively). Patients with HER-2/neu positive tumors presented shorter survival rates (P = 0.06). Patients with response to CMF showed a better survival over non-responders independent of Her-2/neu status. Patients with the combination of response to CMF and Her-2/neu negative tumors presented the best outcome. On the other hand, the association of no response to CMF and positive Her-2/neu score was statistically related to poor DFS and OS. Conclusions CMF indication is independent of Her-2/neu status. We have not received any financial support for the development of this study. The authors thank Edurne Arriola for the assistance in the correction of the paper.     

荧光原位杂交法对胃癌组织HER-2基因状态的检测

目的:比较荧光原位杂交(FISH)法与免疫组织化学(IHC)染色法检测胃癌组织HER-2基因状态的一致性.方法:选择本课题组前期IHC染色法检测775例胃腺癌标本中HER-2蛋白表达为(2+)及(3+)的病例,应用FISH法对HER-2基因扩增情况进行验证.结果:FISH结果显示,86例HER(3+)标本中,60例存在...     

Coexpression of HER-2/neu and p53 is associated with a shorter disease-free survival in node-positive breast cancer patients

Breast cancer tissue was examined for overexpression of HER-2/neu and p53 oncogene proteins. Samples from 105 breast cancer patients were investigated by Western-blot analysis and their relationship to other established markers and clinical outcome was examined. In 21.0% of the cases HER-2/neu was overexpressed, and in 46.7% the p53 protein level was increased. Expression of these two oncogene products was closely correlated. Overexpression of both oncogenes was associated with larger tumour size and negative hormone receptor. The percentage of HER-2/neu and p53 overexpression was higher in node-positive patients, although statistical evaluation was not significant. While overexpression of HER-2/neu as well as p53 in node-positive patients was associated insignificantly with shorter disease-free survival, a significant difference could be documented when the disease-free survival of patients with overexpression of both oncogene proteins was compared to that of patients with no overexpression.     

Clinicopathologic significance of HER-2/neu protein expression and gene amplification in gastric carcinoma

AIM:To study the HER-2/neu protein expression and gene amplification in gastric carcinoma and their relation.METHODS:One hundred and forty-five formalin-fixed and paraffin-embedded tumor tissue samples from Chinese gastric carcinoma patients were studied with immunohistochemistry(IHC)and fluorescence in situ hybridization(FISH)methods.Clinicopathologic data about all patients were collected.RESULTS:The levels of HER-2 3+,HER-2 2+and HER21+were measurable in 6.9%,8.3%and 17.2%of the samples,respectively.No H...     

neu mutation in schwannomas induced transplacentally in Syrian golden hamsters by N-nitrosoethylurea: high incidence but low allelic representation

 Peripheral nerve tumors (PNT) and melanomas induced transplacentally on day 14 of gestation in Syrian golden hamsters by N-nitrosoethylurea were analyzed for activated oncogenes by the NIH 3T3 transfection assay, and for mutations in the neu oncogene by direct sequencing, allele-specific oligonucleotide hybridization, MnlI restriction-fragment-length polymorphism, single-strand conformation polymorphism, and mismatch amplification mutation assays. All (67/67) of the PNT, but none of the melanomas, contained a somatic missense T → A transversion within the neu oncogene transmembrane domain at a site corresponding to that which also occurs in rat schwannomas transplacentally induced by N-nitrosoethylurea. In only 2 of the 67 individual hamster PNT did the majority of tumor cells appear to carry the mutant neu allele, in contrast to comparable rat schwannomas in which it overwhelmingly predominates. The low fraction of hamster tumor cells carrying the mutation was stable through multiple transplantation passages. In the hamster, as in the rat, specific point-mutational activation of the neu oncogene thus constitutes the major pathway for induction of PNT by transplacental exposure to an alkylating agent, but the low allelic representation of mutant neu in hamster PNT suggests a significant difference in mechanism by which the mutant oncogene acts in this species. Received: 8 October 1998 / Accepted: 7 April 1999     

Combined detection of Her2/neu gene amplification and protein overexpression in effusions from patients with breast and ovarian cancer

Purpose  

Her2/neu protein overexpression and gene amplification is found in 20–30% of breast cancer patients and correlates with poor clinical outcome. Patients who profit from anti-Her2/neu- therapy are routinely selected by examination of tumour specimens using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) separately. Many studies found a good correlation between both methods for score 1+ samples and for score 3+ samples, but not for score 2+ samples. In this study, we examined pleural and ascitic effusions with a combined approach using IHC and FISH on the same cells, under the following aspects: (1) frequency of Her2/neu protein expression and gene amplification in effusions; (2) correlation between score of protein expression and gene amplification; (3) impact of chromosome 17 polyploidy on Her2/neu protein expression.     

Role of P53 and BCL-2 in high-risk breast cancer patients treated with adjuvant anthracycline-based chemotherapy

Purpose: Adjuvant therapy has become an integral component of the management of primary high-risk breast cancer patients. However, a considerable fraction of women receive no benefit from this treatment. This study investigates whether a number of biopathological factors can influence the outcome of patients submitted to adjuvant chemotherapy involving the use of high-dose epirubicin and cyclophosphamide. Methods: One hundred and fifty-seven primary breast cancer patients, considered at high risk according to the St. Gallen Meeting Consensus Conference, were evaluated immunohistochemically for estrogen, progesterone receptors, p53, bcl-2, HER-2/neu, and Ki-67, of which the results were correlated with patient outcome. Results: Results obtained demonstrated that p53 is a significant predictor of disease-free survival (DFS P < 0.0001) and overall survival (OS P=0.0002) both in ductal and lobular carcinomas, whereas bcl-2 expression seems to be of prognostic value only in lobular carcinomas (DFS P=0.01; OS P=0.02). Conclusions: This data indicates that in high-risk breast cancer patients the immunohistochemical evaluation of p53 and bcl-2 may be of clinical value in distinguishing different responses to adjuvant anthracycline-based chemotherapy. Received: 4 October 1999 / Accepted: 10 April 2000     

A phase II study of weekly high-dose 5-fluorouracil and leucovorin plus biweekly alternating doxorubicin and cisplatin for advanced gastric carcinoma

On the basis of recent clinical data suggesting that high-dose continuous 5-fluorouracil (5-FU) is able to overcome resistance to 5-FU bolus application in gastric carcinoma, a phase II study was performed to evaluate the activity and toxicity of weekly high-dose 5-FU and leucovorin plus biweekly alternating doxorubicin and cisplatin as the first-line treatment in patients with advanced gastric carcinoma. Between October 1995 and September 1997, 24 consecutive patients with locally advanced (n = 4) or metastatic (n = 20) gastric carcinomas were treated with a combination of 500 mg/m² leucovorin as a 2-h infusion, followed by 2.0 g/m² 5-FU as a 24-h continuous infusion once weekly for 6 weeks, plus 20 mg/m² doxorubicin as a bolus application and 50 mg/m² cisplatin as a 1-h infusion, week 1, 3 and 5 (FLAP regimen). Response, toxicity and survival data were evaluated. A total of 20 patients were evaluable for response and 24 for toxicity. Objective responses were observed in 11 patients (55%) with no complete remission. Four patients (20%) showed stabilization and 5 patients (25%) experienced progressive disease. The median time to disease progression was 8 months and the overall duration of survival was 14 months. Myelosuppression was significant. In 2 patients, grade 4 WHO thrombocytopenia and leukopenia/anaemia respectively were registered, but there were no treatment-related deaths. We conclude that the weekly alternating FLAP regimen is effective in advanced gastric carcinoma with tolerable toxicity. However, significant myelotoxicity and frequent hospitalization suggest that FLAP should not be preferred to other regimens used in metastatic disease. Currently we intend to establish this regimen in the neoadjuvant setting in patients with primary unresectable localized gastric carcinomas. Received: 15 January 1998 / Accepted: 28 January 1998     

Activation of neu by missense point mutation in the transmembrane domain in schwannomas induced in C3H/HeNCr mice by transplacental exposure to N -nitrosoethylurea

Transplacentally initiated schwannomas in mice and rats arise preferentially in the Gasserian ganglion of the trigeminal nerve and spinal root ganglia, while those of the Syrian golden hamster most commonly occur subcutaneously. Rat and hamster schwannomas almost invariably contain a mutationally activated neu oncogene. In rat schwannomas, the mutant allele predominates, while the relative abundance of mutant alleles is very low in hamster nerve tumors. We investigated whether neu is mutated in mouse schwannomas and whether the pattern and allelic ratio of the mutation resemble those for the hamster or the rat. Pregnant C3H/HeNCr mice received 0.4 μmol N-nitrosoethylurea/g body weight on day 19 of gestation. Ten trigeminal and one peripheral nerve schwannomas developed in 11 of the 201 offspring. Missense T → A transversion mutations were detected in the neu transmembrane domain in eight of ten schwannomas analyzed, as determined by MnlI digestion of polymerase chain reaction products. The mutant allele was predominantly detected in two tumors and was abundant in six others. Transfection of eight out of ten mouse tumor DNAs into hamster cells yielded transformed foci; seven out of eight contained mutant mouse neu. Mouse schwannomas closely resembled those of rats both in the preferred anatomical site and in the mutant/wild-type neu allele ratios. Received: 13 January 1999 / Accepted: 15 June 1999     

Tumor Pathology and Long-Term Survival in Emergency Colorectal Cancer

PURPOSE Patients who have an emergency operation for colorectal cancer have poorer long-term survival outcomes compared with elective patients. This study was designed to define the role of tumor pathology as a basis for the differences in survival outcomes. METHODS There were 1,537 elective and 286 emergency patients who had an operation for bowel cancer from 1997 to 2003. Tumor pathology and survival data collected prospectively for these patients were compared by modes of presentation. RESULTS Excluding 30-day mortality, emergency patients as a whole had a five-year all-cause survival rate of 39.2 percent compared with 64.7 percent for elective patients P < 0.0001 they also had more advanced Dukes C and D tumors (P < 0.0001). The rates of early T1 and T2 cancers were 4.7 percent for the emergency and 25 percent for the elective group. Emergency cases had more lymph node-positive patients and N2 patients (57.1 vs. 41.8 percent and 26.6 vs. 15.9 percent, respectively; P < 0.0001). Curatively resected emergency colon patients again had more advanced Dukes staged tumors (P < 0.0001) with a five-year survival rate of 51.6 percent compared with 75.6 percent for elective patients P < 0.0001. On stage-for-stage analysis, the survival rates for curatively resected Dukes B and C colon cancers remained worse for emergency patients (P = 0.003 and P = 0.0002, respectively). Both emergency Dukes B and C groups had more T4 cases (21.5 vs. 10.6 percent; P = 0.017 and 26.4 vs. 15 percent; P = 0.016, respectively). CONCLUSION Advanced tumor pathology is a basis for poor long-term survival in emergency colorectal cancers. Reprints are not available.     

Clinical usefulness of telomerase activity and telomere length in the preoperative diagnosis of gastric and colorectal cancer

It has been reported that telomerase activity and telomeric reduction can be detected in many human cancers. Although it is well known that telomerase activity and telomere length have important implications for cancer biology, their clinical usefulness in the preoperative diagnosis of gastric and colorectal cancer has not been elucidated. Therefore, we examined telomerase activity and telomere length in gastric and colorectal cancer using tissue samples obtained by fiberscopy. Telomerase activity was measured by a telomeric repeat amplification protocol (TRAP). Although telomerase activity was detected in 1/12 (8%) cases of gastric polyp and in 2/9 (22%) cases of colorectal polyp, its positivity in gastric cancer and colorectal cancer was 7/10 (70%) and 21/26 (81%; P < 0.0003 and P < 0.0001, respectively). Telomere length was analyzed by Southern blotting, and telomeric reduction in gastric cancer was significantly greater than that in gastric polyp (P < 0.0003). However, there was no telomeric reduction between colorectal cancer and colorectal polyp. The results of the present study indicate that determination of telomerase activity and telomere length may serve as a useful method for preoperative diagnosis of gastric and colorectal cancer. Received: 16 October 1998 / Accepted: 2 February 1999     

Gastric cancer in very young adults: apropos four patients and a review of the literature

Whether gastric cancer in young adults differs from gastric cancer in older patients has been a controversial issue. It has long been suspected that young patients with gastric cancer have different biological features with a more aggressive course of disease and a poorer prognosis than older patients. This, however, has not been firmly substantiated. We report on the clinical course of four patients (three female and one male) with locally advanced (n  =  1) or metastasized (n  =  3) non-resectable gastric cancer diagnosed under the age of 29 years (23, 25, 27, 28 years). Prior to diagnosis, all three women had recently been pregnant (1–22 months). Diagnosis was endoscopically biopsy-proven and staging work-up was performed by primary explorative surgery (n  =  1), laparoscopy and explorative surgery (n  =  1) or CAT scan and ultrasound (n  =  2). The delay between initial symptoms and diagnosis was 8–22 weeks (median, 10 weeks). The histology was signet-ring cell (n  =  2) or undifferentiated (n = 2) gastric cancer. All patients had the diffuse type of gastric cancer according to Lauren. Patients were treated with the FLAP polychemotherapy regimen consisting of leucovorin, 5-fluorouracil, doxorubicin and cisplatinum, as previously reported. The best response after chemotherapy was partial in two patients. Two patients showed progressive disease. Secondary surgery was performed in three responding patients (one of them responded only locally). One patient achieved no evidence of disease after complete tumor resection (R0). In two patients surgery was palliative (R2/exploration). Three patients died 6, 4 and 8 months after diagnosis. One patient is still alive. In our series, very young adults with gastric cancer had adverse clinical and pathological features. In accordance with other reports, we observed a predominance of female patients and a possible association with recent pregnancies. Though the delay between the first symptoms and diagnosis in our patients was no different from that reported for older patients, special emphasis should be given to prompt referral and diagnostic investigations, ensuring the diagnosis of gastric cancer early in the course of disease. Received: 3 August 1999 / Accepted: 8 September 1999     

Lymphoma-associated hemophagocytic syndrome: clinical features and treatment outcome

The clinical features and prognostic factor of lymphoma-associated hemophagocytic syndrome (LAHS), diagnosed according to World Health Organization classification, were investigated by reviewing the clinical records of 29 patients between September 1994 and September 2006. Compared with patients with T or natural killer (NK)/T cell LAHS, patients with B cell LAHS were older (p = 0.022), were less likely to exhibit disseminated intravascular coagulation (DIC; p = 0.011), and had less direct involvement of bone marrow (p = 0.03). Clinical response was achieved in 15 (65.2%) and complete remission (CR) was achieved in 4 (17%) of 23 patients who received chemotherapy. Four patients received high-dose chemotherapy and autologous stem cell transplantation (A-SCT), and three of these four patients showed CR. The median survival was 36 days (95%CI, 20.2–51.8). Univariate analysis showed that poor performance status (p = 0.028), T or NK/T cell lymphoma (p = 0.016), presence of jaundice (p = 0.063), the presence of DIC (p = 0.002), and poor clinical response to treatment (p < 0.001) predicted poor overall survival. These data suggest that the clinical features differ significantly between B cell LAHS and T or NK/T cell LAHS. Intensive treatment including high-dose chemotherapy and A-SCT should be investigated. A-Reum Han and Hye Ran Lee contributed equally to this study.     

Clinical significance of HER-2/neu expression in colon cancer]

BACKGROUND/AIMS: The HER-2/neu protein is involved in normal cell proliferation and tissue growth because it is extensively homologous and related to epidermal growth factor receptor. As a prognostic marker, HER-2/neu is used to forecast the clinical course and poor outcome in breast cancer. As a predictive marker, HER-2/neu is used to predict the therapeutic response to adjuvant chemotherapy and endocrine therapy in breast cancer. In this study, we investigated the relationships between clinical and pathologic characteristics of tumor and prognosis according to the HER-2/neu expression in colon cancer. This study was conducted for the future introduction of Herceptin therapy for colon cancer patients. METHODS: Overexpression of HER-2/neu was examined by semiquantitative standardized immunohistochemical staining kit in 88 patients with colon cancer. The patients underwent curative surgery at the Kangbuk Samsung Hospital. RESULTS: Overexpression of HER-2/neu was detected in 11 (12.5%) of 88 patients. Tumors with positive HER-2/neu staining showed a tendency for higher rates of nodal metastasis and poor mean survival (1,646 +/- 269 vs 2,631 +/- 141 days) and 5-year survival (65.5% vs 78.9%). CONCLUSIONS: Tumors with positive HER-2/neu staining showed a tendency for higher rates for nodal metastasis and poor clinical survival rate.     

Clinicopathological variables predicting HER-2 gene status in immunohistochemistry-equivocal (2+) invasive breast cancer

Background and objective

Human epidermal growth factor receptor-2 (HER-2) gene status is crucial to guide treatment decisions regarding the use of HER-2-targeted therapies in breast cancer. An invasive breast cancer with HER-2 2+ score is regarded as HER-2 status equivocal and should further determine by fluorescent in situ hybridization (FISH), which is considered the standard test for HER-2 status. Here, we aimed to establish a risk score to allow for prediction of the presence of HER-2 gene status.

Methods

A total of 182 HER-2 2+ by immunohistochemistry (IHC) invasive breast cancer cases were enrolled in this study. The association between clinicopathological variables like age, sex, tumor grade, hormone receptor (HR) status, P53 and proliferation index (Ki67), and FISH result using US Food and Drug Administration (FDA) criteria was evaluated. Also, we compared the HER-2 FISH results using FDA criteria and 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline.

Results

The study population had a median age of 48 years (range, 29-78 years). Estrogen receptor (ER) was expressed in 131 (72.0%) patients. 73.1% of patients (133/182) were progesterone receptor (PR) positive. The median Ki67 value was 20% (range, 3-90%). There was good agreement between the FDA and 2013 ASCO/CAP guideline. Sixty-three of all patients were HER-2 FISH amplified (positive) based on FDA criteria. Tumors with HER-2 amplified were more likely to harbor ER negative (58.8% vs. 25.2%, P<0.001) or PR negative (57.1% vs. 26.3%, P<0.001) or P53 negative (44.8% vs. 29.8%, P=0.048). A significant high level of Ki67 was detected in HER-2 amplified groups (P=0.006). We created a risk score that comprised HR, P53 and Ki67. A significant association between risk score and HER-2 FISH amplification was observed (χ²=30.41, P<0.001).

Conclusions

This novel immunohistochemical risk score could be highly useful to predict the presence of HER-2 gene status in invasive breast cancer.     

Bax and Bcl-2 expressions predict response to radiotherapy in human cervical cancer

The ratio of Bcl-2 to Bax expression determines survival or death following an apoptotic stimulus. In order to establish a new predictor of the outcome of treatment for human cervical carcinoma, we investigated the relationship between the expressions of the Bax and Bcl-2 proteins and the response to radiotherapy after the administration of 10.8 Gy. Methods: A total of 44 patients with histologically proven carcinoma of the uterine cervix, including three with recurrent cervical stump carcinomas, were treated with definitive radiotherapy. The presence of mutations in exons 5–8 of the p53 gene was analyzed by a single-strand conformation polymorphism analysis and DNA sequencing. Results: Forty patients were found to have wild-type p53, and the remaining four had mutant p53. The Bax and Bcl-2 protein expressions prior to radiotherapy did not correlate with response and survival. However, the Bax and Bcl-2 protein expressions after radiotherapy correlated with both response and survival. Bax-positive tumors showed significantly better responses than the Bax-negative tumors after 10.8 Gy radiation (P = 0.0002). In contrast, the Bcl-2-positive tumors showed significantly poorer responses than the Bcl-2-negative tumors after radiation (P = 0.002). Increased Bax expression after the 10.8 Gy radiotherapy was found to be correlated with good survival (P = 0.04). In contrast, increased Bcl-2 expression after such radiotherapy was correlated with poor survival (P = 0.002). Conclusion: The levels of Bax and Bcl-2 expression after 10.8 Gy radiotherapy are useful prognostic markers in patients with human cervical carcinoma. Received: 11 March 1998 / Accepted: 22 May 1998     

Identification of Patients with High-Risk Stage II Colon Cancer for Adjuvant Therapy

Purpose Adjuvant therapy for Stage II colon cancer remains controversial but may be considered for patients with high-risk features. The purpose of this study was to assess the prognostic significance of commonly reported clinicopathologic features of Stage II colon cancer to identify high-risk patients. Methods We analyzed a prospectively maintained database of patients with colon cancer who underwent surgical treatment from 1990 to 2001 at a single specialty center. We identified 448 patients with Stage II colon cancer who had been treated by curative resection alone, without postoperative chemotherapy. Results With median follow-up of 53 months, 5-year disease-specific survival for this cohort was 91 percent. Univariate and multivariate analyses identified three independent features that significantly affected disease-specific survival: tumor Stage T4 (hazard ratio (HR), 2.7; 95 percent confidence interval (CI), 1.1–6.2; P = 0.02), preoperative carcinoembryonic antigen >5 ng/ml (HR, 2.1; 95 percent CI, 1.1–4.1; P = 0.02), and presence of lymphovascular or perineural invasion (HR, 2.1; 95 percent CI, 1–4.4; P = 0.04). Five-year disease-specific survival for patients without any of the above poor prognostic features was 95 percent; five-year disease-specific survival for patients with one of these poor prognostic features was 85 percent; and five-year disease-specific survival for patients with ≥2 poor prognostic features was 57 percent. Conclusions Patients with Stage II colon cancer generally have an excellent prognosis. However, the presence of multiple adverse prognostic factors identifies a high-risk subgroup. Use of commonly reported clinicopathologic features accurately stratifies Stage II colon cancer by disease-specific survival. Those identified as high-risk patients can be considered for adjuvant chemotherapy and/or enrollment in investigational trials. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007. Reprints are not avaliable.