Biomedical subjects

B Iacopetta

Publications and source records attributed to B Iacopetta.

At least 37 records · Page 2Linked to original sources

PubMed2001

Microsatellite instability is a predictive marker for survival benefit from adjuvant chemotherapy in a population-based series of stage III colorectal carcinoma.

Tumors with the microsatellite instability (MSI) phenotype appear to comprise a biologically and clinically distinct group of colorectal carcinomas (CRC). MSI+ has been associated with favorable prognosis; however, it is not clear whether this is because MSI+ tumors are inherently less aggressive or because they are more sensitive to chemotherapy. We investigated the prognostic and predictive significance of this molecular alteration along with its association with nodal burden in a large, population-based cohort of stage III CRC patients. Eight hundred seventy-six stage III CRC patients with long median follow-up (76 months) were included in the study. MSI status was determined by screening for deletions in the BAT-26 mononucleotide repeat. Systemic adjuvant fluoropyrimidine-based chemotherapy was delivered to 266 patients (30%). MSI+ was more common in tumors from female patients and tumors that originated in the proximal colon. It was predictive of excellent survival benefit from chemotherapy but was not associated with better prognosis for patients who did not receive treatment. Lower nodal burden was a prognostic factor for improved survival. MSI+ was associated with lower nodal burden in the overall group (P = 0.02, chi 2 test) but not for patients who received chemotherapy. In stage III CRC, MSI+ was not prognostic in nonadjuvant-treated patients, suggesting that the biological behavior of MSI+ tumors in the absence of chemotherapy is the same as MSI- tumors. Tumors with the MSI+ phenotype appear to be more sensitive to chemotherapy, as observed by improved survival for patients receiving this treatment. MSI along with other molecular markers could be used in the future for a more refined selection of CRC patients to receive fluoropyrimidine-based chemotherapy.

Aged↗

PubMed2001

P53 alteration and microsatellite instability have predictive value for survival benefit from chemotherapy in stage III colorectal carcinoma.

PURPOSE: We recently presented evidence for tumor site and gender-specificity in the survival benefit from adjuvant chemotherapy in Stage III colorectal cancer (CRC). In the current study, we examined whether p53 alteration or the microsatellite instability (MSI) phenotype provide additional predictive information in CRC patients. EXPERIMENTAL DESIGN: A retrospective series of 891 Stage III CRC patients with negative surgical margins was investigated. Thirty percent (270 of 891) received postoperative adjuvant chemotherapy with curative intent and comprising of 5-fluorouracil/levamisole. Adjuvant treatment and nontreatment patient groups were well matched for tumor site, grade, p53 alterations, and MSI. Surgical tumor specimens were investigated for p53 overexpression using immunohistochemistry and for p53 mutation and MSI using single-strand conformation polymorphism analysis. The predictive value of these markers was evaluated by comparing the survival of adjuvant-treated and nonadjuvant treated patients. RESULTS: A strong inverse correlation was observed between p53 alteration and MSI (P < 0.0001). In univariate analysis, the factors of sex, site, p53 alteration, and MSI were each strong predictors of a survival benefit from chemotherapy. Multivariate analysis revealed that chemotherapy provided maximal survival benefit for female patients (P = 0.005) and for patients whose tumors contained normal p53 (P = 0.041). Males whose tumors contained a p53 alteration and were negative for MSI appeared not to benefit from chemotherapy. CONCLUSIONS: Our findings suggest that p53 alteration and MSI could be clinically useful molecular predictive markers for the identification of CRC patients who might benefit from 5-fluorouracil-based chemotherapy.

Adult↗

PubMed2000

Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer.

BACKGROUND: Adjuvant chemotherapy can improve 5-year survival in Dukes' C colorectal carcinoma. Improved selection of patients who will respond to adjuvant treatments is required. We investigated whether site of tumour origin, sex, and presence of microsatellite instability (MSI) phenotype were associated with a survival benefit from adjuvant chemotherapy. METHODS: We analysed data for 656 consecutive patients with Dukes' C colorectal carcinoma, with median follow-up of 54 months (range 7-104) and mean age 66.7 years (SD 12.9). We screened tumour samples by PCR for deletions in the BAT-26 mononucleotide repeat to establish MSI status. Details of chemotherapy and survival were obtained by review of hospital and health-department records. Adjuvant chemotherapy (fluorouracil and levamisole) was given with curative intent to 272 (42%) patients. FINDINGS: Striking survival benefits were seen for patients who had right-sided tumours and who received adjuvant chemotherapy compared with those who did not (48 vs 27% alive at end of study [95% CI 0.25-0.56], p<0.0001), for women (53 vs 33% [0.25-0.56], p<0.0001), and for patients with MSI tumours (90 vs 35% [0.01-0.53], p=0.0007). MSI-positive tumours were slightly more frequent in women than in men (10 vs 7%). Right-sided tumours were more frequently MSI positive than left-sided tumours (20 vs 1%). Men with right-sided tumours benefited from chemotherapy (37 vs 12% [0.24-0.69], p=0.0007) but men with left-sided tumours did not. INTERPRETATION: The survival benefits seen in patients treated with adjuvant chemotherapy suggest that data from previous trials of adjuvant chemotherapy should be reassessed and the predictive value of MSI status confirmed. Validation of our results will allow better selection of patients for chemotherapy.

Aged↗

PubMed2000

Relating genotype and phenotype in breast cancer: an analysis of the prognostic significance of amplification at eight different genes or loci and of p53 mutations.

Breast cancer heterogeneity can be related directly to its variability at the genetic level. Thus, tumor genotyping could be a valuable approach to define breast tumor subtypes. It has been shown that it is possible to delineate subgroups of breast tumors according to specific sets of DNA amplifications. The aim of the present work was to study the prognostic significance of these DNA amplifications. We studied DNA amplification at eight genes or loci (AIB1, CCND1, EMS1, ERBB2, FGFR1, MDM2, MYC, and RMC20C001) as well as p53 mutations in a series of 640 breast cancer patients who had not received presurgical therapy and analyzed the correlations with survival DNA amplification was assessed by Southern blotting and was scored positive when exceeding three to five copies. Mutations in the p53 gene were searched by four-color fluorescent single. strand conformational polymorphism, using an automated sequencer. Of the nine genetic alterations tested, four (CCND1, EMS1, FGFR1, and p53 mutations) showed a significant association with reduced disease-free (DFS) and/or overall survival (OVS) in the unselected set of patients by univariate test. Correlations for p53 were found only when selecting mutations in exons 5 or 7. Analysis of node-negative and -positive subgroups of patients showed that MDM2 amplification and p53 mutations bore prognostic significance in node-negative patients, whereas amplification of CCND1, EMS1, and FGFR1 correlated with poor outcome in node-positive patients. Multivariate analysis on an unselected set of patients retained significance for the amplification of EMS1, FGFR1, and MDM2 with DFS, of CCND1 with OVS, and of RMC20C001 with both DFS and OVS. Interestingly, stratified analysis according to nodal status confirmed results obtained in the univariate tests: significance of MDM2 amplification and p53 mutations in node-negative and that of CCND1, EMS1, and FGFR1 in node-positive patients. We also observed an association between the number of genetic alterations observed in a tumor and poor prognosis. Patients with two or more amplified loci had a worsened outcome. Strongly correlating coamplifications such as CCND1 and FGFR1, as well as ERBB2 and MYC, were associated with a significant reduction of patient survival, thus indicating cooperative effects. Our data support the idea that genetic alterations in breast cancer are not only helpful for phenotyping purposes, but can also represent powerful prognostic indicators in the clinical practice.

Breast Neoplasms↗

PubMed2000

Can p53 alterations be used to predict tumour response to pre-operative chemo-radiotherapy in locally advanced rectal cancer?

PURPOSE: To examine whether p53 tumour suppressor gene alterations can be used to predict tumour response to pre-operative chemo-radiation in locally advanced rectal cancer in terms of reduction in tumour size and local failure. METHODS: p53 alterations were studied in pre-treatment biopsy specimens of rectal carcinomas from 48 patients by immunohistochemistry (IHC) and polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) gene mutation analysis. Pre-operative pelvic radiotherapy was delivered with four fields, 45 Gy to the ICRU point in 25 fractions over 5 weeks. A radio-sensitising dose of 5-fluorouracil (500 mg/m(2)) was delivered concurrently for 6 days of the 5-week schedule (days 1, 2, 3 and days 22, 23 and 24). Total meso-rectal excision was planned 4 to 6 weeks from completion of pre-operative treatment. Response to therapy was assessed by macroscopic measurement of the surgical specimen by a pathologist who was unaware of the pre-treatment tumour size or of the p53 status. RESULTS: IHC evidence of p53 protein accumulation was found in 40% of tumours, p53 gene mutation in 35% and p53 alteration (either or both changes) in 46%. The average reduction in tumour size was 53% in the group with 'wild-type' p53 (IHC-/SSCP-) and 63% in the group with altered p53 (either IHC+ or SSCP+; P=0.18). No significant differences in tumour size reduction or local failure were observed in the groups with p53 overexpression or p53 mutation compared with normal. CONCLUSIONS: p53 alteration detected by IHC or SSCP analysis is not a clinically useful predictor of local response to pre-operative adjuvant therapy in advanced rectal carcinoma.

Adenocarcinoma↗

PubMed2000

Prognostic significance of TP53 gene mutation in 995 cases of colorectal carcinoma. Influence of tumour site, stage, adjuvant chemotherapy and type of mutation.

Previous studies on the prognostic significance of TP53 gene alterations in colorectal cancer (CRC) have led to conflicting results. The present study investigated the prognostic significance of TP53 gene mutation in a very large series of 995 Dukes' B and C CRC patients, the majority of whom did not receive chemotherapy. Mutations were found in 385 (39%) cases and were not associated with tumour stage, histological grade, patient age or sex. Significantly more mutations were found in tumours from the left-sided colon compared with those from the right side (43% versus 34%, P=0.006). TP53 gene mutation had no prognostic value in the overall series or in different site or stage subgroups. None of the different types of TP53 gene mutation showed prognostic value. A trend for association with worse survival was observed in the patient subgroup that received adjuvant chemotherapy (Hazard Ratio (HR) 1.4, 95% confidence interval (CI) 0.89-2.21, P=0.15). These results indicate that mutation of the TP53 gene is not a useful prognostic marker for CRC patients who do not receive adjuvant chemotherapy. Further study is required to determine whether different types of TP53 mutation might be of value in predicting the response of CRC patients to chemotherapy.

Adult↗

PubMed2000

Routine analysis of p53 mutation in clinical breast tumor specimens using fluorescence-based polymerase chain reaction and single strand conformation polymorphism.

Improved prognostic and predictive markers in breast cancer management would help considerably in therapeutic decision making, particularly in patients with early-stage breast cancer. Tumor factors currently used for prognostication and management decisions are tumor size, histologic type and grade, axillary lymph node status, and estrogen receptor content. The discovery of various somatic genetic alterations in breast cancer has raised the possibility that these may provide additional and independent prognostic and predictive information. Alterations of the p53 tumor suppressor gene in particular have received the most attention as potential prognostic and predictive factors. In multivariate analysis, p53 gene mutation is consistently associated with a two- to threefold increased risk of relapse and death from breast cancer. One of the major reasons preventing the introduction of p53 mutation as a routine marker to assist in therapeutic decision making is the lack of a simple, reproducible, and inexpensive assay. In the present study the authors optimized a polymerase chain reaction-based mutation screening method, fluorescence-single strand conformation polymorphism (F-SSCP), that allows p53 status to be assessed accurately and reproducibly in routinely handled, formalin-fixed and paraffin-embedded tumor specimens. The frequency of p53 mutation observed using F-SSCP in a consecutive series of invasive ductal breast carcinomas was 17% (28/164). The authors propose that the prognostic and predictive values of p53 mutation in breast cancer should be further evaluated in prospective, randomized studies using this standardized technique.

Adult↗

PubMed2000

p53 gene mutation, microsatellite instability and adjuvant chemotherapy: impact on survival of 388 patients with Dukes' C colon carcinoma.

Two common genetic alterations in colon carcinoma, p53 mutation and microsatellite instability (MSI), were investigated to determine their prognostic importance for cancer-specific survival and response to adjuvant chemotherapy in patients with Dukes' C colon cancer. The p53 tumour suppressor gene encodes for a nuclear phosphoprotein involved in cellular response to DNA damage, while MSI is a characteristic feature of tumours with defective DNA mismatch repair. The cellular response mechanisms to DNA-damaging agents in tumours with mutant p53 or MSI may as a consequence differ, and this might translate into different outcomes following adjuvant chemotherapy. A consecutive series of 388 Dukes' C colon carcinomas with 5-year median follow-up was analysed for p53 mutation and for MSI (in proximal/transverse carcinomas only) using polymerase chain reaction single-strand conformation polymorphism. The incidence of p53 mutation was 28% in all carcinomas while that of MSI in proximal/transverse carcinomas was 19%. One hundred and thirty-three patients (34%) received adjuvant chemotherapy (5-fluorouracil/levamisole) with curative intent. The presence of p53 mutation did not predict for survival in either the treated or untreated groups. The presence of MSI in the proximal/transverse colon carcinoma group was associated with significantly better 5-year survival: 58 versus 32% (p = 0.015, log rank test). This was largely due to better survival observed in the MSI subgroup that received adjuvant chemotherapy (p = 0.017, log rank test). Further work in prospective, randomised clinical trials investigating the effects of adjuvant therapy should consider incorporating MSI status in order to determine whether this is an independent predictive factor for survival and/or response to adjuvant chemotherapy.

Aged↗

PubMed2000

Routine detection of the replication error phenotype in clinical tumor specimens using fluorescence-SSCP.

Almost all tumors from patients with hereditary non-polyposis colon carcinoma and approximately 10%-15% of sporadic colon and gastric carcinomas contain widespread deletions within mono- and dinucleotide repeat sequences in their DNA. This is referred to as the replication error (RER+) phenotype and, in the case of colon carcinoma, is often associated with an improved tumor prognosis and possibly also with response to chemotherapy. The RER+ status of tumors is usually determined by examining several dinucleotide and mononucleotide repeats for size variations when compared with the matching normal DNA. Alternately, the identification of deletions within BAT-26, a quasi-monomorphic polyadenine tract within the hMSH2 gene, has been shown to establish the RER+ status of tumors with greater than 99% accuracy and without the need for normal DNA. Here, we use fluorescent PCR in combination with single strand conformation polymorphism analysis to detect deletions in BAT-26. This technique provides a sensitive, rapid, reproducible and inexpensive assay suitable for the routine identification of RER+ status in clinical tumor specimens.

DNA Repair↗

PubMed2000

Prognostic significance of mutations to different structural and functional regions of the p53 gene in breast cancer.

Alteration to the p53 tumor suppressor gene is associated with more aggressive disease in breast cancer, as evidenced by the shortened survival of patients with mutation. Data obtained from in vitro experiments suggest that mutations to different structural and functional domains of p53 may give rise to different effects on its biological activities, notably transactivational and apoptotic properties. We evaluated the prognostic significance of various types of p53 mutation in a series of 178 tumors identified by PCR-single-strand conformational polymorphism screening as containing a mutant gene. Mutations within exon 4 were associated with particularly poor prognosis, possibly relating to the importance of this region in apoptosis. Mutations that caused denaturation of the protein structure were also associated with poor survival, again perhaps because of effects on apoptosis. In contrast, patients with mutations in the DNA contact region showed similar survival to that of patients with normal p53, suggesting a less important role for p53-mediated transactivation in determining tumor aggressiveness. Other mutation groups associated with poor prognosis were single-base substitutions and transversion mutations. Mutations in exon 6, exon 7, or the "hotspot" codons (175, 245, 248, 273) were associated with only a small reduction in patient survival compared with normal p53. These results allow some insight to be gained into the functional importance of various p53 domains in terms of their influence on overall patient survival. Further work is required to determine whether these domains are also important in influencing the response of breast tumors to adjuvant therapies.

Amino Acid Substitution↗

PubMed1999

Variable mutation frequencies in coding repeats of TCF-4 and other target genes in colon, gastric and endometrial carcinoma showing microsatellite instability.

Frameshift mutations in genes containing mononucleotide repeats are often observed in cancers exhibiting a high frequency of microsatellite instability (MSI-H). Several tumor types, including colorectal, gastric, and endometrial carcinomas, display this phenotype in a significant proportion of cases. We recently showed in a large series of MSI-H colorectal tumors that approximately 40% of them exhibited frameshift mutations in an (A)9 tract within the coding region of the TCF-4 gene, a crucial member of the APC/beta-catenin/TCF pathway. In the present study, we have examined MSI-H cancers from other primary tumor sites for mutations in this new target gene. Two of 22 (9%) MSI-H primary gastric cancers and none of 23 MSI-H endometrial primary tumors and cell lines were found to have a 1 bp deletion in the TCF-4 repeat. In the same series of tumors we also looked for frameshift mutations in other coding repeats localized within the TGF beta-RII, BAX, IGFIIR, hMSH3 and hMSH6 genes. Our results suggest that the TCF-4 gene, in a similar manner to some of these latter genes, is differentially altered in MSI-H tumors from different primary sites.

Base Sequence↗

PubMed1999

Frequent frameshift mutations of the TCF-4 gene in colorectal cancers with microsatellite instability.

About 15% of sporadic colorectal cancers show microsatellite instability (MSI) due to the inactivation of mismatch repair genes and are termed MSI-H tumors. In these tumors, frameshift mutations in coding repeats have been found within the TGFbeta-RII, BAX, and IGFRII genes that are probably involved in their progression. In the present work, we report frequent mutations in TCF-4, another target gene for instability. TCF-4 codes for a transcription factor that is a crucial member of the adenomatous polyposis coil (APC)/beta-catenin/T-cell factor (TCF) pathway. Fifty percent (4 of 8) of human MSI-H colorectal cell lines and 39% (19 of 49) of MSI-H colorectal primary tumors were found to have a 1-bp deletion in an (A)9 repeat within the coding region of this gene. In contrast, a frameshift mutation was found in only 1 of 56 non-MSI colorectal tumors and in none of 16 non-MSI colorectal cancer cell lines. These results suggest that TCF-4 frameshift mutations are selected for and play a role in colorectal MSI-H tumorigenesis. Depending on different reading frames due to alternatively spliced TCF-4 mRNA, the (A)9 repeat normally codes for several isoforms that could serve as modulators of TCF-4 transcriptional activity. The deletion of one nucleotide in this repeat could change TCF-4 transactivating properties by modifying the respective proportions of the different isoforms.

Colorectal Neoplasms↗

PubMed1999

Hypermethylation of the MYF-3 gene in colorectal cancers: associations with pathological features and with microsatellite instability.

Myf-3 is the human homologue of the murine Myo-D1 gene involved in muscle-cell differentiation. Using Southern blot analysis, we examined methylation of Myf-3 in histologically normal colonic mucosae, adenomas and carcinomas from a large series of patients with primary colorectal cancer. Hypermethylation of this gene in comparison with normal mucosa was observed in 88% of adenomas and in 99% of carcinomas. The pattern of Myf-3 methylation was similar in different areas of the same tumour, suggesting that methylation imbalances occur before the bulk of clonal-cell expansion. Significantly increased levels of Myf-3 methylation were observed in tumours which were more invasive, located in the proximal colon or from older patients. Patients whose tumours had extensive methylation showed a trend for shortened survival, though this was probably related to their being more invasive. Extensive methylation was significantly more frequent in tumours with microsatellite instability. Further work is required to determine whether the hypermethylation of Myf-3 observed in colorectal cancers is a specific alteration with functional significance or whether it reflects non-specific methylation imbalances occurring early during tumorigenesis.

Adenoma↗

PubMed1999

TP53 gene mutation status in pretreatment biopsies of oesophageal adenocarcinoma has no prognostic value.

Identification of markers which help to predict response to treatment and overall survival at the time of diagnosis would assist in the management of patients with oesophageal adenocarcinoma. In the present study we investigated the prognostic significance of mutations to the TP53 tumour suppressor gene in a large, consecutive series of oesophageal adenocarcinomas. The incidence of TP53 mutation determined by molecular analysis of endoscopic biopsy specimens was 36% (49/135). No statistically significant difference was observed in patient survival according to the TP53 status of the tumour biopsy. The median survival time for patients with mutation was 12 +/- 1 months compared with 14 +/- 2 months for patients with TP53. These results demonstrate that mutation of the TP53 gene is not a useful predictive marker for patient survival in oesophageal adenocarcinoma.

Adenocarcinoma↗

PubMed1999

p53 protein overexpression is a prognostic indicator of poor survival in stage I endometrial carcinoma.

The prognostic value of p53 protein overexpression was investigated in a large series of early stage endometrial carcinomas with long follow-up (n=179, median follow-up 147 months). P53 overexpression was detected in 10 cases (5.6%). At the end of the study period, 30% (3/10) of patients with p53 protein overexpression had died of their disease compared to 6.5% (11/169) of those without overexpression. Multivariate analysis revealed that only myometrial invasion (RR 2. 1; 95% CI=1.2-3.6; P=0.001) and p53 overexpression (RR 9.5; 95% CI=2. 5-36.8; P=0.007) were independent predictors of survival. These results suggest that immunohistochemical evaluation of p53 protein overexpression provides strong prognostic information for the outcome of endometrial carcinoma patients with early stage disease.

Adult↗

PubMed1999

P53 alterations have no prognostic or predictive significance in Dukes' C rectal carcinomas.

We investigated the prognostic significance of p53 alterations in a consecutive series of 122 Dukes' C rectal carcinomas with a median patient follow-up period of 56 months. One third of patients were treated with post-operative adjuvant chemotherapy. Overexpression of p53 protein was observed in 42% (50/118) of cases using immunohistochemical analysis and mutation of the p53 gene in 38% (47/122) using single strand conformation polymorphism technique. Neither p53 overexpression nor mutation were associated with significantly worse patient survival in the overall group or in the subgroup of 35 patients who received standard post-operative chemotherapy with 5-fluorouracil and levamisole. Our results do not support the use of p53 alteration as a clinically useful prognostic marker for the overall survival of rectal cancer patients or for predicting their response to chemotherapy.

Adult↗

PubMed1998

Rapid and nonisotopic SSCP-based analysis of the BAT-26 mononucleotide repeat for identification of the replication error phenotype in human cancers.

Microsatellite instability is an important new form of genetic alteration that characterizes tumors of the replication error phenotype (RER+). The RER status of tumors has been determined until now by analyzing several microsatellite loci for size variations compared with matching normal DNA. This has been done by separating isotopically labeled PCR products on denaturing gels. We recently showed that deletions within BAT-26, a polyadenine tract within the hMSH2 gene, could be used to establish the RER status of tumors without the need for matching normal DNA. We now propose a rapid and nonisotopic method of determining RER status based on PCR-SSCP analysis of the BAT-26 poly(A) tract. Compared with conventional means of examining RER+, this method reduces the PCR and gel manipulations involved by 10-fold. Size variations of as little as 2 bp in the BAT-26 sequence were readily detected using mini-sized, silver-stained SSCP gels run for 2.5 h. The incidence of RER+ detected in 183 right-sided colonic, 121 gastric, and 123 endometrial carcinomas was 20%, 10%, and 5% respectively, using this method. Frameshift mutations in the mononucleotide repeat of the TGF-beta RII gene were found in 86% (42/49) of RER+ but less than 1% (1/237) of RER- colon and gastric tumors identified by BAT-26 analysis. Our results demonstrate that nonisotopic PCR-SSCP of the poly(A) BAT-26 tract is a specific, sensitive and rapid method for determining the RER status of human tumors.

DNA Replication↗

PubMed1998

Analysis of p53 gene mutation by polymerase chain reaction-single strand conformation polymorphism provides independent prognostic information in node-negative breast cancer.

Controversy continues regarding the prognostic utility of detection of p53 gene abnormalities in node-negative breast cancer. To resolve this, we used a rapid and nonisotopic PCR-single strand conformation polymorphism method to screen for mutations in exons 4-8 of the p53 gene in primary tumors from 422 node-negative breast cancer patients. The prevalence of p53 mutation in the exons tested was 18%. p53 mutation was significantly associated with several markers of poor prognosis including larger tumor size, high tumor grade, low hormone receptor content, increased expression of MIB-1 (Ki-67), amplification of the HER-2/neu oncogene, and accumulation of the p53 protein. After a median duration follow-up period of 74 months, the parameters of tumor diameter > or =20 mm, HER-2/neu oncogene amplification, and p53 mutation were found to be associated with a statistically significant shortened duration of disease-free and overall survival, but not the parameters of tumor grade, hormone receptor levels, or p53 expression. The poor prognosis associated with p53 mutation was observed primarily in patients with a tumor diameter of > or =20 mm. In multivariate analysis, p53 mutation was a risk factor for increased risk of recurrence and death from breast cancer independent of tumor size, hormone receptor levels, HER-2/neu amplification, and MIB-1 expression. We conclude that a relatively simple and rapid single strand conformation polymorphism method of determining p53 mutation status in node-negative breast cancers can provide independent prognostic information.

Adult↗