P53 Gene Alterations Research Articles

Mutations of p53 tumor-suppressor gene in angiosarcoma.

Transgenic mice deficient for the p53 gene were reported to frequently develop angiosarcoma (AS), suggesting that alterations in the gene are associated with tumorigenesis of AS. However, little is known about genetic changes, including p53 gene alterations, in human AS because of its rarity. We analyzed p53 mutations on paraffin-embedded specimens from 33 patients with AS by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by direct sequencing. Age of patients ranged from 18 to 91 (median 70) years, with a male to female ratio of 1.5:1. Sites of tumor were the head in 13 patients, the trunk in 4, the extremities in 4, the heart in 4, bones in 2 and others in 6. PCR-SSCP revealed aberrant mobility shifts of bands in 17 cases: 11 in exon 5, 5 in exon 7 and 4 in exon 8. Direct sequencing on these 17 cases revealed a total of 20 mutations. The frequency of p53 mutations was different by site of tumors: 7 of 13 in head, all 4 in extremities, 2 of 4 in heart and none of 4 in trunk. Our findings suggest that occurrence of p53 mutation is a major pathway for development of human AS.

P53 gene alterations are associated with a decreased responsiveness to neoadjuvant chemotherapy in human breast cancer

Recent evidence indicates that alterations of the p53 tumor suppressor gene can modulate the response of tumor cells to DNA-damaging agents and increase drug resistance. To evaluate whether p53 alterations affect response to chemotherapy in breast cancer, we examined the p53 status before and after treatment of primary tumors from 44 patients who received neoadjuvant chemotherapy. p53 status was determined by gene mutations and by mRNA expression levels. Eleven patients (25%) showed alterations in the p53 gene. Comparison of the clinical response between subgroups with or without p53 alterations revealed that p53 alterations were strongly associated to clinical resistance to chemotherapy (p<0.001).

CHRONIC ULTRAVIOLET EXPOSURE-INDUCED p53 GENE ALTERATIONS IN SENCAR MOUSE SKIN CARCINOGENESIS MODEL

Alterations of the tumor suppresser gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Senear mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12/24 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → C, and one A → T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sam ple. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Senear mouse skin.

CHRONIC ULTRAVIOLET EXPOSURE-INDUCED p53 GENE ALTERATIONS IN SENCAR MOUSE SKIN CARCINOGENESIS MODEL

Abstract Alterations of the tumor suppresser gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Senear mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12/24 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → C, and one A → T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sam ple. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Senear mouse skin.

Expression of the cyclin dependent kinase inhibitor p21WAF1/CIP1 in oesophageal squamous cell carcinomas.

To elucidate the role of CDK inhibitor p21WAF1/CIP1 in human oesophageal squamous cell carcinomas, we examined its expression immunohistochemically using surgically resected tissues from 25 patients, and have analyzed the relationship with alteration of p53 gene (F-SSCP analysis), proliferative activity (Ki-67 labelling index), frequency of apoptosis (in situ DNA nick end labelling), and degree of differentiation. P21 expression was observed in 11 cases (44%) with a percentage of positive cells ranging between 1% and 10%. Of the 25 cases, 4 cases showed > 5% of positive cells. As for the relationship with p53 gene, all 7 p53-mutation positive cases were negative for p21 expression, whereas 11 out of 18 mutation negative cases showed positive for p21 expression. As for the relationship with degree of tumour differentiation, 6 out of 8 well differentiated type cases showed positive for p21 expression. By contrast, all 8 cases of poorly differentiated type were negative for p21 expression. Frequency of apoptotic cells was significantly higher in p21 positive cases than negative cases although Ki-67 labelling index was almost the same regardless of the expression of p21. P21 expressing cells were distributed mainly in the middle layers of the invading nests, especially around the keratinization, which was almost similar to the distribution of apoptotic cells. Our results suggest that expression of p21 in human oesophageal squamous cell carcinomas is induced by a p53-dependent pathway and affects apoptosis and differentiation of carcinoma cells.

P53 protein accumulation and p53 gene alterations (RFLP, VNTR and p53 gene mutations) in non-invasive versus invasive human transitional bladder cancer

Eleven non-invasive and 24 invasive transitional cell bladder cancers were analysed for molecular alterations to the p53 gene and nuclear accumulation of the p53 protein. 9% (1/11) of non-invasive rumours and 21% (5/24) of invasive tumours revealed nuclear accumulation in more than 50% of the tumour cells. PCR analysis of D17S30 showed loss of heterozygosity (LOH) in invasive tumours (3/24; 12%). Two invasive tumours harboured point mutations in exon 6 and exon 7, respectively (8%). Our results indicate that p53 protein overexpression correlates with tumour progression, p53 gene mutations and LOH detected by PCR.

P53 protein expression in adenoid cystic carcinoma of the head and neck

Forty-one adenoid cystic carcinomas were investigated retrospectively with the polyclonal antibody CM-1 against the p53 protein and the results compared with clinicopathological parameters and the proliferative activity estimated by Ki-67 expression. p53 acted as a significant explanation variable in simple linear regression with Ki-67 as the dependent variable (r=0.39, p<0.02). High p53 expression was observed in tumors with violated margins during primary surgery. No significant correlations were demonstrated with other clinicopathological parameters or treatment outcome. Alterations in the p53 gene may be responsible for increased proliferative activity in the tumors, but elevated antigen expression has little prognostic value.

The expression of MDM2 and p53 protein breast carcinoma

We studied the expression of MDM2 protein and p53 protein in 67 cases of the breast carcinoma. The result demonstrated no significant relationship between the MDM2 protein expression and any of the clinicopathological parameters except for the estrogen receptor status (p=0.033). Furthermore, in p53 protein negative cases, there was a significant relationship between MDM2 protein expression and the ER status (p=0.027). This study showed the expression of ER to be associated with MDM2 protein in p53 protein negative breast carcinoma. These results thus suggested that an investigation of both p53 and MDM2 gene alteration revealed precise information regarding breast carcinoma.

Alterations of the p16INK4A gene in human ovarian cancers.

The p16INK4A gene, which encodes the cell-cycle regulatory protein cyclin-dependent kinase 4 inhibitor, is a putative tumor-suppressor gene. We examined p16 gene alterations in 30 primary ovarian cancers and 11 ovarian cancer cell lines. Five of the primary cancers (16.7%) had lost both p16INK4A genes. In addition, four cancers (13.3%) contained five kinds of missense mutations and a one-base deletion. Three cell lines had homozygous deletions of p16 genes, and one cell line had multiple intragenic mutations. There was also suppressed transcription of the p16 gene in one cell line. Some point mutations occurred in the conserved ankylin consensus region. These observations suggest that p16 is a functional target for ovarian carcinogenesis and that p16 alterations occurred in the primary cancers.

Modulation of alterations in p53 tumor suppressor gene and its association with activation of ras proto-oncogenes during chemoprevention of colon cancer

Previously, we reported (Carcinogenesis 15: 1317-1323, 1994) a high rate of activating point mutations in I ns proto-oncogenes in azoxymethane (AOM)-induced colon tumors, and a significant suppression of these mutations by dietary administration of chemopreventive agents, D,L-alpha-difluoromethylornithine (DFMO) and piroxicam. To understand the role of p53 tumor suppressor gene in chemoprevention of colon cancer and to study the association of p53 gene alterations with activation of ras genes, we determined point mutations in conserved regions (exons 5-9) of p53 gene and analyzed the occurrence of double event of ms activation acid p53 mutation. Groups of male F344 rats were fed the modified AIN-76A diet containing 0, 4000 ppm DFMO, or 150 ppm piroxicam and administered s.c. AOM at a dose rate of 15 mg/kg body wt, once weekly, for 4 weeks. Vehicle controls received s.c. equal volume of normal saline. Animals were sacrificed 32 weeks after the last AOM or saline injection and their grossly visible colon tumors were analyzed to determine p53 mutations by PCR amplification based single strand conformation polymorphism (SSCP) and direct DNA sequencing. Our results demonstrate that about 57% tumors from animals fed the control diet contained predominantly missense but also nonsense mutations, whereas only 30% tumors from animals on piroxicam diet, and none (0%) from animals fed the DFMO diet had similar mutations. Analysis of data revealed that about half of the tumors from animals on control diet possessed both ms and p53 mutations together, only 27% of colon tumors from animals on piroxicam diet and none of the tumors from animals on DFMO diet exhibited both ms and p53 mutations. These results indicate that the administration of piroxicam, a non-steroidal anti-inflammatory drug, and DFMO, a irreversible inhibitor of ornithine decarboxylase, may inhibit selective proliferation of initiated cells containing activated las and/or mutant p53. Dietary DFMO exerted more pronounced inhibition of selective amplification of initiated cells containing mutated ras and/or p53.

Altered expression of p53 and mdm-2 proteins at diagnosis is associated with early treatment failure in childhood acute lymphoblastic leukemia.

To determine whether potential alteration in p53 function through p53 gene mutation or mdm-2 overexpression correlates with early treatment failure in childhood acute lymphoblastic leukemia (ALL). Diagnostic marrow samples from 34 children were analyzed for p53 gene alterations by western blot and SSCP/DNA sequence analysis and for mdm-2 overexpression by western blot analysis. These samples were derived from two groups of children with ALL: 17 good outcome patients who are in long-term continuous complete remission and 17 poor outcome patients who did not achieve a complete remission or relapsed within 6 months of achieving remission. Two children within the poor outcome group were found to have p53 gene mutations. Furthermore, five poor outcome patients were shown to have greater than 10-fold overexpression of mdm-2 protein compared with the mean level of mdm-2 protein measured in the good outcome group. Aberrant p53 protein expression was found in only one good outcome patient, whereas no good outcome children were found to have elevated levels (> 10-fold) of mdm-2 protein. We show for the first time that potential alteration in p53 function in childhood ALL is more common (P = .036) in cases of early treatment failure than in children who remain in long-term continuous remission.

Alterations of the p16 gene in head and neck cancer: frequency and association with p53, PRAD-1 and HPV.

Alterations, especially homozygous deletions, of the putative tumor suppressor gene, p16 (p16INK4A, MTS1, CDKN2) have been found in tumor cell lines from a variety of neoplasms. Recent studies have reported frequent p16 gene deletions in cell lines from squamous cell carcinomas of the head and neck (SCCHN), although the prevalence of alterations was variable in primary tumors. This study determined the prevalence of point mutations and deletions of the p16 gene in 33 SCCHN. In addition, the association of p16 gene alterations and abnormalities of p53, PRAD-1 (cyclin D1), and the presence of human papillomavirus (HPV) was examined. We found an overall prevalence of p16 alterations of 36% (nine deletions, three single base substitutions, including one polymorphism). Seven tumors (of 29, 24%) had an alteration of p16 and p53; five (of 33, 15%) had alterations of p16 and PRAD-1; three (of 29, 10%) had alterations of all three genes. In addition, of the five tumors with human papillomavirus detected, only one also had a p16 gene alteration. The results indicate a potentially important role for the p16 gene in head and neck tumorigenesis. In addition, the presence of tumors with multiple somatic gene alterations suggest a possible interaction in the dysregulation of the cell cycle.

Mutations of the p16 gene product are rare in prostate cancer.

The p16 gene product is a negative regulator of cell cycle and has been shown to be deleted or mutated in a number of tumor cell lines and primary tumors. The role of p16 in prostate cancer is not defined. Prostate cancer tissues and cell lines were evaluated for p16 gene alterations. Five metastatic prostate cancer cell lines were analyzed for p16 gene structure and its expression by Southern and Northern blot analyses. Forty-one DNA specimens from 18 microdissected primary tumor specimens, adjacent normal tissues, and cell lines were amplified by polymerase chain reaction for p16 protein coding and splice junction sequences. Mutations were analyzed by single strand conformation polymorphism and DNA sequencing. DU 145 cell line exhibited a missense mutation in codon 84 (GAC to TAC). With the exception of previously reported polymorphism, no mutation was detected in p16 coding or splice junction sequences in primary prostate cancer specimens. Inactivation of p16 gene by mutations in the protein coding sequence does not play a major role in the genesis of primary prostate cancer.

Mutations of the p16 gene product are rare in prostate cancer

BACKGROUND The p16 gene product is a negative regulator of cell cycle and has been shown to be deleted or mutated in a number of tumor cell lines and primary tumors. The role of p16 in prostate cancer is not defined. Prostate cancer tissues and cell lines were evaluated for p16 gene alterations. METHODS Five metastatic prostate cancer cell lines were analyzed for p16 gene structure and its expression by Southern and Northern blot analyses. Forty-one DNA specimens from 18 microdissected primary tumor specimens, adjacent normal tissues, and cell lines were amplified by polymerase chain reaction for p16 protein coding and splice junction sequences. Mutations were analyzed by single strand conformation polymorphism and DNA sequencing. RESULTS DU 145 cell line exhibited a missense mutation in codon 84 (GAC to TAC). With the exception of previously reported polymorphism, no mutation was detected in p16 coding or splice junction sequences in primary prostate cancer specimens. CONCLUSIONS Inactivation of p16 gene by mutations in the protein coding sequence does not play a major role in the genesis of primary prostate cancer. Prostate 30:188–194, 1997. © 1997 Wiley-Liss, Inc.

P53 alterations in breast cancer of the Parsi ethnic group

Mutations in p53 are the most common genetic abnormality yet found in human cancers. p53 mutations vary among tumor types, ranging from 0-60% in major cancers. The frequency of p53 mutations in breast cancer averages around 25%. The incidence rate and the type of mutations at specific codons seem to be influenced by geographical location as well as racial and ethnic specificities. Women of the Parsi ethnic group living mostly in defined geographical areas around metropolitan Bombay are reported to have a markedly high incidence of breast cancer. In the present work, the p53 gene alterations in the Parsis were investigated using SSCP analysis. The results confirm an earlier observation that over 60% of the Parsi breast tumors harbour p53 alterations. This figure is higher than that observed in other communities. The relevance of the finding in the light of the high breast cancer incidence in the Parsis is discussed.

Clinicopathologic analysis of k-ras, p53, and ERBB-2 gene alterations in pulmonary adenocarcinoma.

We compared PCR-SSCP detected mutations of k-ras (codon 12) and p53 (exons 5-8) to ERBB-2 immunostaining and clinicopathologic features in 31 pulmonary adenocarcinomas. There were nine tumors (29%) with mutations of ras, 13 tumors (42%) with mutations of p53, and three tumors (10%) with mutations of both. Neither k-ras nor p53 mutation alone was significantly correlated with stage, grade, or survival. However, tumors with k-ras mutation were more frequently associated with an invasive growth pattern, defined as > 30% tumor volume composed of infiltrative nests of cells within desmoplastic, scar-like stroma [< 30% volume invasive--1/13 (8%) with k-ras mutation vs. > 30% volume invasive--8/18 (44%) with k-ras mutation, p = 0.02]. Accordingly, k-ras mutations were observed in only 1/9 (15%) predominantly bronchoalveolar or papillary tumors versus 6/22 (28%) acinar or scar carcinoma tumors. All three patients with combined k-ras/p53 mutation had advanced stage (III/IV) at presentation and died of the disease. In contrast to k-ras, staining for ERBB-2 was more frequently observed in tumors exhibiting < 30% invasive growth pattern (12/13, 92%) than in tumors with > 30% invasive growth pattern (10/18, 56%, p = 0.03). ERBB-2 immunoreactivity was more frequent in Stage I (14/15, 93%) versus Stage II-IV (8/16, 50%) cases, but it did not correlate with survival. There was a reciprocal relationship between k-ras mutation and ERBB-2 staining; only 4/9 (44%) k-ras mutated cases were ERBB-2 positive versus 18/22 (82%) cases without k-ras mutation (p = 0.005). In contrast, 8/13 cases with p53 mutation were ERBB-2 positive. We conclude that well-differentiated and less invasive papillary and bronchoalveolar tumors are more often ERBB-2 positive/k-ras negative (i.e. at codon 12), whereas less well differentiated acinar or scar carcinomas are more often ERBB-2 negative/k-ras mutated at codon 12. These findings imply that the divergent histogenesis of pulmonary adenocarcinoma may reflect specific differences in genetic pathology.

P53 protein expression in ductal carcinoma in situ (DCIS) of the breast.

Abnormalities in p53 gene expression have been implicated in many inherited and sporadic forms of malignancies in humans. Immunohistochemical staining using monoclonal antibody D0-7 for the p53 protein expression was performed in 81 cases of pure DCIS, 14 benign breast lesions and 2 cases with normal breast tissue. Expression of p53 protein was detected in 15 (18.5%) cases of pure DCIS. Thirteen (25%) of the 52 comedo type DCIS showed p53 protein expression compared with 2 (6.9%) of the 29 non-comedo types (P < 0.02). p53 protein expression was also associated with high nuclear grade (P < 0.001) and high mitotic index (P < 0.05). The pattern of p53 protein staining was diffuse in one comedo type DCIS, regional in 6 comedo types, and focal in the remaining 8 cases (6 comedo type and 2 micropapillary type DCIS). The patient with comedo type DCIS showing diffuse staining has a family history of breast cancer in the first and second degree relatives (sister and maternal aunt). Clinical follow-up data was available in 52 cases. Follow-up period ranged from 9 to 55 months. Three patients, who were primarily treated by local excision, have had a documented local recurrence in the form of residual tumor within a short interval of 5 to 11 months. In all these three patients both the original and the recurrent tumors are negative for p53 protein expression. The difference in the local recurrence rate between p53 positive (0/15) and p53 negative (3/37) cased does not reach statistical significance (p > 0.05). We interpret that the local tumor recurrence in these three cases within a short period after primary excision is due to the presence of residual tumor at the excision site and is independent of the p53 gene alteration. It is concluded that p53 protein expression in DCIS is associated with comedo subtype, high nuclear grade, and high mitotic index, and is a promising new parameter to evaluate the cellular biology and prognosis of DCIS.

Change of Cell-cycle Related Proteins and Tumor Suppressive Effect in Non-small Cell Lung Cancer Cell Line after Transfection of p16(MTS1) Gene

Background : It is clear that deregulation of cell cycle progression is a hallmark of neoplastic transformation and genes involved in the /S transition of the cell cycle are especially frequent targets for mutations in human cancers, including lung cancer. p16 gene product, one of the G1 cell-cycle related proteins, that is recently identified plays an important role in the negative regulation of the the kinase activity of the cyclin dependent kinase (cdk) enzymes. Therefore p16 gene is known to be an important tumor suppressor gene and is also called MTS1 (multiple tumor suppressor 1). No more oncogenes have been reported to be frequently related to multiple different malignancies than the alterations of p16 gene. Especially when it comes to non-small cell lung cancer, there was no expression of p16 in more than 70% of cell lines examined. And also it is speculated that p16 gene could exert a key role in the development of non-small cell lung cancer. This study was designed to evaluate whether p16 gene could be used as a candidate for gene therapy of non-small cell lung cancer. Methods : After the extraction of total RNA from normal fibroblast cell line and subsequent reverse transcriptase reaction and polymerase chain reaction, the amplified p16 cDNA was subcloned into eukaryotic expression plasmid vector, pRC-CMV. The constructed pRC-CMV-p16 was transfected into the NCI-H441 NSCLC cell line using lipofectin. The changes of G1 cell-cycle related proteins were investigated with Western blot analysis and immunoprecipitation after extraction of proteins from cell lysates and tumor suppressive effect was observed by clonogenic assay. Results : (1) p16(-) NCI-H441 cell line transfected with pRC-CMV-p16 showed the formation of p16 : cdk 4 complex and decreased phosphorylated Rb protein, while control cell line did not. (2) Clonogenic assay demonstrated that the number of colony formation was markedly decreased in p16(-) NCI-H441 cell line transfected with pRC-CMV-p16 than the control cell line. Conclusion : It is confirmed that the expression of p16 protein in p16 absent NSCLC cell line with the gene transfection leads to p16 : cdk4 complex formation, subsequent decrease of phosphorylated pRb protein and ultimately tumor suppressive effects. And also it provides the foundation for the application of p16 gene as a important candidate for the gene therapy of NSCLC.

P53 gene alterations in human tumors: perspectives for cancer control.

Alterations of the p53 gene are found in the majority of human tumors (Caron de Fromentel and Soussi 1992; Hollstein et al. 1991; Tominaga et al. 1992; Levine et al. 1991; Greenblatt et al. 1994). The encoded nuclear phosphor protein is a transcription factor that binds to a specific DNA motif and trans activates genes controlling cell cycle checkpoints, DNA repair, and cell death (Clarke et al. 1993; Lane 1993; Lowe et al. 1993; El Deiry et al. 1994). The p53 protein can also play a role in maintaining the integrity of the genome by sensing DNA changes, by affecting DNA repair processes, and perhaps by influencing homologous recombination events or DNA replication (Kastan et al. 1992; Yin et al. 1992; Livingstone et al. 1992; Lane 1994; Cox et al. 1995; Jayaraman and Prives 1995; Wang et al. 1995).

Early Occurrence and Prognostic Significance of p53 Alteration in Primary Carcinoma of the Fallopian Tube

The pathogenesis of primary carcinoma of the fallopian tube (PCFT) is poorly understood. Tumor suppressor p53 gene alterations are common in human malignancies, but their role in the tumorigenesis and survival of PCFT is undefined. The objectives of this study were to define the occurrence and prognostic role of p53 alteration in PCFT and to examine the efficiency of immunohistochemistry (IHC) in detecting p53 alteration in PCFT. Fifty-two PCFT and 10 normal fallopian tubes were examined for p53 alteration by IHC and polymerase chain reaction–single-strand conformation polymorphism (PCR–SSCP). The Kaplan–Meier method was used to derive the survival function, while the log-rank test was used to compare curves for two or more groups. Other patients’ characteristics were analyzed by two-tailed Fisher's exact tests. IHC correlated well with PCR–SSCP with 100% sensitivity and 83.3% specificity for detecting p53 alteration in this study. Thirty-one of 52 (57%) PCFT showed p53 alteration. Alteration of p53 occurred in all stages of PCFT with a similar incidence in carcinomain situand late-stage disease. Alteration of p53 was related to tumor histologic type. Significant survival difference was noted between advanced and early clinical stages but no such difference was identified among different tumor grades. Compared to the p53-nonaltered group, the presence of p53 alteration in PCFT was related to significantly decreased patient survival (RR = 6.8, 95% CI = 2.9–16.2) in multivariate analysis. In the subgroup of patients with residual tumor after surgery, those with p53-altered tumors had a significantly decreased survival compared to those with p53-nonaltered group (RR = 7.4, 95% CI = 1.9–28.2). Alteration of p53 is common and IHC is an efficient method to detect p53 alteration in PCFT. Shorter survival is associated with p53 alteration which is an independent marker for the disease in this study. Alteration of p53 may be an early event in tubal tumorigenesis and may play an important role in the development of PCFT. Whether detection of p53 alteration may serve as an indicator of high-risk patients for whom more aggressive adjuvant chemotherapy may be considered needs to be explored in the future.