Altered Expression of the Cell Cycle Regulatory Molecules pRb, p53 and MDM2 Exert a Synergetic Effect on Tumor Growth and Chromosomal Instability in Non-small Cell Lung Carcinomas (NSCLCs)

Gorgoulis, V. G.; Zacharatos, P.; Kotsinas, A.; Mariatos, G.; Liloglou, T.; Vogiatzi, T.; Foukas, P.; Rassidakis, G.; Garinis, G.; Ioannides, T.; Zoumpourlis, V.; Bramis, J.; Michail, P. O.; Asimacopoulos, P. J.; Field, J. K.; Kittas, Ch.

doi:10.1007/BF03402115

Molecular Medicine

Table 1 Summary of pRb, p53, MDM2 status, kinetic parameters, ploidy status and patients’ clinicopathological features

From: Altered Expression of the Cell Cycle Regulatory Molecules pRb, p53 and MDM2 Exert a Synergetic Effect on Tumor Growth and Chromosomal Instability in Non-small Cell Lung Carcinomas (NSCLCs)

Sample	Sex	Age	Smoking	pRb Status				p53 Status		p53 Status	MDM2 Status				AI	Ploidy	Clinicopathological Features
				IHC	AIm D13S153	IHC	SSCP Analysis	Defective Exon	Gene Mutation	Amino Acid Substitution	AIm D17S179E	IHC	mRNA Level	%	%		Histology	LN	Stage	Patients “Follow Up”*
19	M	70	YES	No	LOH	N	−				ho	N	NE	NI	10,6	D	AD	NO	I	34+
20	M	66	YES	No	LOH	N	+	9	not examined		NI	N	NE	24,6	3,5	D	SQ	NO	I	34+
22	M	70	YES	No		N	−					N	NE	46,6	1,5	D	AD	NO	I	34+
31	M	64	YES	No	LOH	N	−				ho	N	OE	21,2	3	D	AD	NO	I	10
36	M	57	NO	No		N	−					N	NE	28,8		A	AD	YES	III	10
45	M	57	YES	No	ho	N	−				ho	N	NE	32,9	8,9	D	AD	YES	II	27
46	M	68	NO	No	H	N	−				ho	N	NE	NI		D	AD	NO	I	29+
51	M	48	YES	No	H	N	−				H	N	NE	20,0	2,9	D	AD	YES	II	15
54	M	65	YES	No	LOH	N	−				LOH	N	NE	32,2	3,1	NI	SQ	NO	I	28+
62	M	57	YES	No	ho	N	+	8	codon 270, TTT -> ATT	F -> F	LOH	N	NE	41,4	1,4	A	SQ	NO	I	13
66	M	58	YES	No	LOH	N	−				LOH	N	NE	33,3	2,3	A	SQ	YES	II	3
80	M	75	YES	No		N						N	NE	29,2	1,2	D	SQ	NO	I	64+
81	M	68	YES	No		N						N	NE	19,0	1,1	D	AD	NO	I	48+
3	M	61	YES	No		N	−					P	OE	28,3	1,6	A	SQ	NO	I	37+
21	M	70	YES	No	H	N	−				LOH	P	OE	34,5	NI	D	SQ	YES	III	1
30	M	75	YES	No		N	−					P	OE	28,8	5,2	D	UL	NO	I	32+
32	M	42	YES	No		N	+	5	codon 163, TAC -> TGC	Y -> C		P	OE	26,4	0,7	A	AD	YES	III	30+
37	M	71	NO	No	LOH	N	−				NI	P	OE	28,9	3,2	A	AD	YES	II	12
39	M	56	YES	No	H	N	−				ho	P	OE	54,0	0,9	D	SQ	YES	III	9
40	M	54	YES	No		N	−					P	NE	31,0		A	UL	NO	I	18
41	M	67	YES	No		N	+	4	codon 110, CGT -> CT	FS		P	OE	38,0	0,5	A	SQ	NO	I	30+
43	M	60	NO	No		N	+	4	codon 60, CCA -> CCT	P -> P		P	OE	21,4	3,5	A	AD	YES	II	30+
44	M	72	NO	No	H	N	+	6	codon 213, CGA -> _GA	FS	ho	P	OE	22,3	0,7	A	AD	YES	III	14
50	M	62	NO	No	ho	N	−				H	P	NE	18,1	1,4	D	AD	YES	II	27
79	M	72	YES	No		N						P		33,7		A	SQ	YES	II	14
82	M	74	YES	No		N						P		28,7		A	SQ	YES	II	40+
83	M	59	YES	No		N						P		13,7	2,6	D	AD	YES	III	69+
84	M	47	YES	No		N						P		40,9	0,6	D	SQ	NO	I	67+
8	F	69	NO	No		P	+	7	codon 248, CGG -> TGG	R -> W		N	NE	31,0	1,4	D	AD	NO	I	34+
13	M	64	YES	No	H	P	+	7	codon 248 CGG -> CTG	R -> L	ho	N	NE	32,8		D	SQ	YES	III	8
24	M	62	YES	No	ho	P	+	4	codon 74, GCC -> ACC	A -> T	LOH	N	NE	26,7	0,8	NI	SQ	NO	I	N/A
38	M	53	YES	No		P	−					N	NE	39,3	3	A	SQ	YES	III	30+
52	M	72	YES	No	LOH	P	+	8	codon 273, CGT -> CAT	R -> H	LOH	N	NE	39,0	0,6	A	SQ	NO	III	29+
67	M	71	NO	No	H	P	−				ho	N	NE	20,2	0,6	D	AD	NO	I	24+
71	M	67	YES	No		P						N		22,1	1,5	NI	SQ	YES	II	40
72	M	73	YES	No		P						N		NI		D	AD	YES	II	17
73	M	67	YES	No		P						N		26,2		D	SQ	−	−	−
74	M	74	YES	No		P						N		20,5	1,5	D	AD	NO	I	69+
5	M	61	YES	No		P	+	7	codon 244, GGC -> TGC	G -> C		P	OE	32,8	6,3	A	AD	YES	III	12
7	M	64	YES	No	LOH	P	+	8	codon 273, CGT -> CTT	R -> L	ho	P	OE	27,2	1,2	A	SQ	YES	II	35+
10	F	68	YES	No	LOH	P	+	4	codon. 93, CTG -> ATG	L -> M	ho	P	OE	40,6	1,8	A	UL	YES	II	9
11	M	70	YES	No	LOH	P	+	8	codon 280, AGA -> ATA	R -> I	H	P	OE	36,0	0,7	A	SQ	NO	I	34+
16	M	63	YES	No	H	P	−				NI	P	OE	4,6	0,8	D	AD	NO	I	7
17	M	64	YES	No	H	P	−				H	P	NE	27,3	1,2	NI	SQ	NO	II	34+
18	M	73	YES	No	H	P	+	7	codon 230, ACC -> AAC	T -> N	LOH	P	OE	43,6	4,8	D	SQ	YES	II	11
26	M	63	YES	No		P	+	6	codon 196, CGA -> CCA	R -> P		P	OE	29,2	0,1	A	AD	YES	II	17
42	M	76	YES	No	LOH	P	+	5	codon 157, GTC -> TTC	V -> F	NI	P	OE	43,8	0,6	A	SQ	YES	III	30+
59	M	65	YES	No	LOH	P	+	5	codon 143, GTG -> GCC	V -> A	LOH	P	OE	30,4		A	AD	NO	I	25
61	M	59	YES	No	LOH	P	−				LOH	P	OE	24,5	1,1	D	AD	YES	III	26+
68	M	61	YES	No		P	−					P	OE	59,1	2,1	A	SQ	YES	II	21
69	F	50	YES	No		P						P	NE	NI	0,9	A	AD	YES	II	23
70	M	66	YES	No		P	+	7	codon 233, CAC -> TAC	H -> Y		P	NE	36,3		D	SQ	NO	I	63
23	M	79	YES	Ab	LOH	N	−				H	N	OE	26,7	2,6	D	AD	YES	II	18
25	M	63	NO	Ab	H	N	−				ho	N	NE	21,3	1,4	D	AD	NO	I	33+
85	M	66	YES	Ab		N						N		NI		NI	SQ	YES	II	109+
86	F	68	YES	Ab		N						N		19,7	0,8	A	AD	YES	II	22
27	M	70	NO	Ab	LOH	N	+	8	codon 282, CGG -> _GG		LOH	P	OE	13,3	3,5	NI	AD	YES	I	14
33	M	59	YES	Ab		N	−					P	OE	40,7	0,8	A	SQ	NO	I	14
34	M	63	YES	Ab		N	−					P	OE	34,7	0,5	D	AD	NO	I	32+
49	M	53	NO	Ab		N	−					P	OE	36,9		D	AD	NO	I	29+
87	M	64	YES	Ab		N						P		23,6	0,5	A	AD	YES	II	10
53	M	60	YES	Ab	LOH	P	+	9	codon 319, AAG -> AAT	K -> N	ho	N	NE	51,2	2,6	A	SQ	YES	III	15
78	M	69	YES	Ab		P						N		26,0	0,7	D	AD	NO	III	72+
1	M	57	YES	Ab	H	P	−				H	P	NE	31,1	4,8	A	AD	YES	III	3
4	M	60	YES	Ab	H	P	+	7	codon 249, AGG -> AGT	R -> S	ho	P	OE		NI	A	UL	NO	I	0
6	M	75	YES	Ab		P	+	5	codon 151, CCC -> CAC	P -> H		P		45,6	0,6	A	SQ	YES	II	35+
9	M	53	YES	Ab	LOH	P	+	7	codon 238, TGT -> TTT	C -> F	ho	P	OE	30,3	12	D	AD	NO	I	35+
12	M	70	YES	Ab		P	+	7	codon 234, TAC -> TGC	Y -> C		P	OE	29,5	0,9	A	SQ	NO	I	35+
14	M	74	YES	Ab	LOH	P	+	7	codon 239, AAC -> ACC	N -> T	ho	P	OE	38,5	1,3	A	SQ	YES	III	8
15	M	69	YES	Ab	LOH	P	+	5	codon 163, TAC -> TGC	Y -> C	LOH	P	OE	40,6	1,1	A	SQ	NO	I	34+
28	M	60	YES	Ab	LOH	P	+	5	codon 157, GTC -> TTC	V -> F	ho	P	OE	40,9	1,5	A	SQ	NO	I	33+
29	M	61	YES	Ab	ho	P	+	4	codon 69, GCT -> GGT	A -> G	ho	P	OE	43,4	2,7	A	UL	YES	III	0
35	M	67	YES	Ab		P	−					P	NE	29,2	0,8	A	AD	YES	I	17
47	M	71	YES	Ab	LOH	P	−				ho	P	OE	54,4	0,5	A	SQ	NO	I	25
48	M	73	YES	Ab		P	+	7	codon 237, ATG -> ATA	M -> I		P		44,0	0,5	D	SQ	NO	III	14
55	M	52	NO	Ab	ho	P	+	8	codon 275, TGT -> TTT	C -> F	ho	P	OE	43,3	0,8	A	AD	YES	II	10
56	M	58	YES	Ab	LOH	P	−				ho	P	NE	47,3	0,4	A	SQ	YES	II	11
57	M	58	YES	Ab	H	P	+	5	codon 153, CCC -> CAC	P -> H	NI	P	OE	40,0	1,8	A	SQ	YES	III	8
58	M	52	NO	Ab	LOH	P	−				ho	P	OE	46,0	0,6	A	AD	YES	II	26+
60	M	64	YES	Ab	LOH	P	−				H	P	OE	38,6	1	A	AD	YES	III	23
63	F	60	YES	Ab		P	−					P	OE	50,6	1	A	AD	NO	III	25+
64	M	62	YES	Ab	LOH	P	−				LOH	P	OE	39,3	1,6	D	AD	NO	I	25+
65	M	56	YES	Ab	ho	P	−				LOH	P	OE	70,4	0,7	A	SQ	YES	II	22
75	F	33	YES	Ab		P						P		39,1	0,5	A	AD	YES	III	0
76	M	51	YES	Ab		P						P		34,0	0,4	A	SQ	YES	II	1
77	M	69	YES	Ab		P						P		42,1	0,3	D	SQ	NO	II	73+
2	M	60	YES	NI	LOH	NI	−				LOH	NI		NI		NI	SQ	YES	III	21

M: Male, F: female; IHC: Immunohistochemistry, No: Normal expression, Ab: Aberrant expression, P: Positive, N: Negative, NI: Non Informative; AIm: Allelic Imbalance analysis, LOH: Loss of Heterozygosity, H: Heterozygous, ho: homozygous; SSCP: Single Strand Conformation Polymorphism analysis, +(−): indicates possible mutation (no mutation), FS: frameshift; NE: Normal Expression, OE: OverExpression; PI: Proliferation Index, AI: Apoptotic Index, D: Diploid, A: Aneuploid; SQ: Squamous cell carcinoma, AD: Adenocarcinoma, UL: Undifferentiated Large cell carcinoma, LN: Lymph Node metastasis.
*in months after surgery, (+) indicates that the patient is alive

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ISSN: 1528-3658

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