TP53 Database: View Prognostic Value of Tumor Variants

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	Prognosis_ID	Topography	Short_topo	Morphology	Country	Population	Region	Development	Institution	Period	InclusionCriteria	Treatment	MedianFU	RangeFU	Cohort	P53_mutation	Parameter_analysed	Association	Result	Ref_ID	Cross_Ref_ID	Title	Authors	S_Ref_Year	Journal	Volume	Start_page	End_page	PubMed	Comment	Tissue_processing	Start_material	Prescreening	Material_sequenced	exon2	exon3	exon4	exon5	exon6	exon7	exon8	exon9	exon10	exon11	Exclude_analysis

	Prognosis_ID	Topography	Short_topo	Morphology	Country	Population	Region	Development	Institution	Period	InclusionCriteria	Treatment	MedianFU	RangeFU	Cohort	P53_mutation	Parameter_analysed	Association	Result	Ref_ID	Cross_Ref_ID	Title	Authors	S_Ref_Year	Journal	Volume	Start_page	End_page	PubMed	Comment	Tissue_processing	Start_material	Prescreening	Material_sequenced	exon2	exon3	exon4	exon5	exon6	exon7	exon8	exon9	exon10	exon11	Exclude_analysis

	1	BREAST	BREAST	Cancer, NOS	Australia	Australia/New Zealand	Western Pacific	More developed regions	Charles Gairdner (Perth), Royal Perth Hospital, Flinders Medical Center (South Australia)	1987-1997	consecutive primary cancers	SU, CX/RX	65.0	1-120	1037	178	survival	associated with bad	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.	1425	969	Prognostic significance of mutations to different structural and functional regions of the p53 gene in breast cancer	Powell B;Soong R;Iacopetta B;Seshadri R;Smith DR;	2000	Clin Cancer Res	6	443	451	10690522			DNA	SSCP	direct	false	false	true	true	true	true	true	false	false	false	false
	2	BREAST	BREAST	Cancer, NOS	Japan	Eastern Asia	Asia	More developed regions	Hokkaido University Hospital, Sapporo	1991-1996	consecutive primary cancers	CX (5FU;TAM;LH-RH)	43.0	6-81	76	30	survival	associated with bad	p53 mutations were associated with a short overall survival (log rank test, p = 0.0319), whereas it was not related to disease-free (recurrence-free) survival. Contact mutants were associated with slightly shorter survival compared with structural mutants. The patients with tumors harboring both p53 mutation and loss of estrogen receptor had the poorest outcome (p = 0.0019 and 0.0075 for overall and disease-free survivals, respectively).	1346	1099	Distinct prognostic values of p53 mutations and loss of estrogen receptor and their cumulative effect in primary breast cancers	Takahashi M;Tonoki H;Tada M;Kashiwazaki H;Furuuchi K;Hamada J;Fujioka Y;Sato Y;Takahashi H;Todo S;Sakuragi N;Moriuchi T;	2000	Int J Cancer	89	92	99	0010719737		frozen	RNA	FASAY	cloned	false	false	true	true	true	true	true	true	true	false	false
	3	BREAST	BREAST	Cancer, NOS	Norway	Northern Europe	Europe	More developed regions	Norwegian Radium Hospital, Oslo	1984-1989	consecutive primary cancers		38.3	0.1-94.1	163	35	survival	associated with bad	TP53 alteration in primary tumour was significantly associated with the following parameters: positive node status, T status > 1, negative oestrogen receptor status, negative progesterone receptor status, presence of ERBB2 gene amplification, and invasive ductal histology. Furthermore, there were statistically significant associations, independent of other prognostic factors, between TP53 alterations in primary tumour and disease-free and overall survival.	234	66	Prognostic significance of TP53 alterations in breast carcinoma	Andersen TI;Holm R;Nesland JM;Heimdal KR;Ottestad L;Borresen AL;	1993	Br J Cancer	68	540	548	0008102535	See also ref 1764, add info from ref 2369	frozen	DNA	DGGE	direct	false	false	false	true	true	true	true	false	false	false	false
	4	BREAST	BREAST	Cancer, NOS	Iceland	Northern Europe	Europe	More developed regions	University Hospital of Iceland, Reykjavik	<1993	consecutive primary cancers		32.0	0-60	109	18	survival	associated with bad	There was a significant association between p53 mutation and low content of estrogen receptor protein in the tumors (P = 0.01). An association with poor prognosis was strongly indicated by mortality rates that were 37.5% among the patients with p53 mutation and 9.4% for the control group (mean follow up, 32 months). P53 mutation was found to be the strongest negative factor against survival in a covariate survival analysis (P = 0.001)	193	193	Somatic p53 mutations in human breast carcinomas in an Icelandic population: a prognostic factor	Thorlacius S;Borresen AL;Eyfjord JE;	1993	Cancer Res	53	1637	1641	0008453635	see also refID-2369	frozen	DNA	DGGE	direct	false	false	false	true	true	true	true	false	false	false	false
	5	BREAST	BREAST	Carcinoma, NOS	Norway	Northern Europe	Europe	More developed regions	Norwegian Radium Hospital, Oslo		localy advanced cancer (T3/4 and/or N2); prospective study	CX (doxo)			90	26	response	associated with bad	Mutations in the TP53 gene, in particular those affecting or disrupting the loop domains L2 or L3 of the p53 protein, were associated with lack of response to chemotherapy (P = 0.063 for all mutations and P = 0.008 for mutations affecting L2/L3, respectively)….	1544	583	Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer	Geisler S;Lonning PE;Aas T;Johnsen H;Fluge O;Haugen DF;Lillehaug JR;Akslen LA;Borresen-Dale AL;	2001	Cancer Res	61	2505	2512	11289122	See also ref 1764	fixed/frozen	DNA	TTGE	direct	true	true	true	true	true	true	true	true	true	true	false
	6	BREAST	BREAST	Cancer, NOS	Sweden	Northern Europe	Europe	More developed regions	University of Uppsala	1987-1989	consecutive primary cancers	SU, RX, CX (5FU, MTX, CP)		0-90	315	69	survival	associated with bad	The p53 status was related to prognosis and effect of adjuvant therapy. p53 mutations in the evolutionary conserved regions II and V were associated with significantly worse prognosis. Update 2005 (Miller LD et al, 2005, PNAS): The classifier (based on proteins' function) separated patients into low and high risk groups with a much higher statistical significance than the sequence-based p53 status alone (p=0,0006 vs; p=0,01). Our analysis of genes involved in the p53 pathway suggests that the p53 expression signature defines some operational configuration of this pathway in breast tumors (more than p53 mutation status alone) that impacts patient survival and therapeutic response.	1641	992	Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy	Bergh J;Norberg T;Sjogren S;Lindgren A;Holmberg L;	1995	Nat Med	1	1029	1034	7489358	See refs 1006 and 2369	frozen	DNA	none	direct	true	true	true	true	true	true	true	true	true	true	false
	7	BREAST	BREAST	Cancer, NOS	The Netherlands	Western Europe	Europe	More developed regions	Rotterdam Cancer Institute	1978-1991	consecutive primary cancers	SU, CX (CMF; CAF); TAM	115.0	47-183	177	53	survival/response	associated with bad	In a Cox univariate analysis, TP53 gene mutation was significantly associated with poor relapse-free survival (RFS: P = 0.02) but not with overall survival (OS: P = 0.07). In a Cox multivariate analysis, including classical prognostic factors, TP53 gene mutation independently predicted poor RFS and OS (RHR = 1.8 and 1.6 respectively). Unexpectedly, the median relapse-free survival of patients with a polymorphism at codon 213 or with a silent mutation was shorter (median 11 months) than the median relapse-free survival of patients with or without a TP53 gene mutation (median 34 or 48 months respectively). In an exploratory subset analysis, mutations in codons that directly contact DNA were related with the poorest relapse-free (P < 0.05) and overall survival (P < 0.02).	1003	1003	Mutations in residues of TP53 that directly contact DNA predict poor outcome in human primary breast cancer	Berns EM;van Staveren IL;Look MP;Smid M;Klijn JG;Foekens JA;	1998	Br J Cancer	77	1130	1136	0009569050		frozen	DNA	SSCP	direct	false	false	false	true	true	true	true	false	false	false	false
	8	BREAST	BREAST	Cancer, NOS	USA	Northern America	Americas	More developed regions	Mayo Clinic, Rochester		consecutive primary cancers; prospective study	SU, CX (CMF, CAF)		0-60	90	32	survival/response	associated with bad	The presence of a p53 gene mutation was the single most adverse prognostic indicator for recurrence (p = 0.0032) and death (p = 0.0001), and was associated with poor response to both adjuvant (p = 0.0001) and palliative (p = 0.006) therapy.	1642	64	A prospective trial of midwest breast cancer patients: a p53 gene mutation is the most important predictor of adverse outcome	Blaszyk H;Hartmann A;Cunningham JM;Schaid D;Wold LE;Kovach JS;Sommer SS;	2000	Int J Cancer	89	32	38	10719728	See also ref 73, 406, 467 and 613	frozen	DNA	none	direct	false	false	true	true	true	true	true	true	true	false	false
	9	BREAST	BREAST	Cancer, NOS	Denmark	Northern Europe	Europe	More developed regions	Aarhus University Hospital	1992-1994	consecutive primary cancers; retrospective study	SU, CX		0-60	315	74	survival	associated with bad	Although TP53 mutation in general was associated with aggressive tumor/patient characteristics, missense mutations outside any conserved or structural domain did not affect the clinical outcome (risk of disseminated disease and death). In contrast, patients with missense mutations affecting amino acids directly involved in DNA or zinc binding displayed a very aggressive clinical phenotype. Null mutations (including missense mutations disrupting the tetramerization domain) and the remaining missense mutations displayed an intermediate aggressive clinical phenotype.	1392		Heterogeneity in the clinical phenotype of TP53 mutations in breast cancer patients	Alsner J;Yilmaz M;Guldberg P;Hansen LL;Overgaard J;	2000	Clin Cancer Res	6	3923	3931	11051239			DNA	DGGE	direct	true	true	true	true	true	true	true	true	true	true	false
	10	BREAST	BREAST	Cancer, NOS	Austria	Western Europe	Europe	More developed regions	Vienna Medical School	1984-1990	consecutive primary cancers; ER pos.	SU, CX (CMF)	107.0	0-168	205	42	survival	associated with bad	p53 mutation served as a statistically significant parameter in predicting disease-free survival in univariate (P = 0.02) and multivariate (P = 0.009) analysis. For overall survival, no significant differences were observed. Patients with tumours that had p53 mutations within the L2/L3 domains of the gene showed no significant difference to those with mutations outside the L2/L3 domains for disease-free survival. For overall survival, mutations in the L2/L3 domains showed a marginally significant difference (P = 0.05) in multivariate analysis, but not in univariate analysis (P = 0.13).	1173		Prognostic significance of mutations in the p53 gene, particularly in the zinc-binding domains, in lymph node- and steroid receptor positive breast cancer patients. Austrian Breast Cancer Study Group	Kucera E;Speiser P;Gnant M;Szabo L;Samonigg H;Hausmaninger H;Mittlbock M;Fridrik M;Seifert M;Kubista E;Reiner A;Zeillinger R;Jakesz R;	1999	Eur J Cancer	35	398	405	0010448289		fixed	DNA	DGGE	direct	false	false	false	true	true	true	true	false	false	false	false

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