Somatic molecular changes and histo-pathological features of colorectal cancer in Tunisia

Table 1 Clinical and histo-pathological characteristics of the 51 colorectal cancer patients n (%)

Characteristic	Patient
Age of onset of the first cancer (range) (yr)	51 (17-85)
≤ 50	25 (49.0)
> 50	26 (51.0)
Sex
Male	30 (58.8)
Female	21(41.2)
Site of the first CRC
Right colon	14 (27.5)
Left colon	16 (31.4)
Rectum	21 (41.2)
TNM tumor stage
I	3 (5.9)
II	24 (47.1)
III	20 (39.2)
IV	3 (5.9)
Others	1 (2.0)
Degree of differentiation
Well	33 (64.7)
Moderate	14 (27.5)
Poor	2 (3.9)
Mucinous CRC	2 (3.9)
Mucinous carcinoma type
≥ 50%	14 (27.5)
≤ 50%	37 (72.5)
Signet ring cell carcinoma	2 (3.9)
Tumor infiltrating lymphocyte
Crohn’s–like reaction	2 (3.9)
Intra epithelial lymphocytes	1 (2.0)
Lymphoïde peritumoral reaction	10 (19.6)
Synchronous CRC	3 (5.9)
Metachronous CRC and HNPCC related cancer	3 (5.9)
Fulfillment of guidelines
Amsterdam	3 (5.9)
Revised Bethesda	22 (43.1)
B1	22
B2	3
B3	11
B4	1
B5	1

CRC: Colorectal cancer; HNPCC: Hereditary nonpolyposis colorectal cancer; TNM: Tumor node metastasis.

Table 2 Statistical analysis of clinicopathological parameters of the 51 colorectal cancer studied tumors as a function of tumoral phenotype n (%)

	Mutation MMR -	Mutation MMR +	Family history of colorectal cancer		P	Ams - and Beth -	Ams - and Beth +	P	Ams (- or +) and Beth +	P
	(n = 6)	(n = 4)	Yes (n = 8)	No (n = 43)		(n = 26)	(n = 22)		(n = 25)
Mutation geminale
MMR+			4	0		0	2		4
MMR-			3	3		0	5		6
Site of tumor (CCR)					NS			NS		NS
Right colon	1	3	5 (63)	10 (23)		5 (19)	9 (41)		10 (40)
Left colon	2	0	1 (13)	14 (33)		8 (31)	7 (32)		7 (28)
Rectum	3	1	2 (25)	19 (44)		13 (50)	6 (27)		8 (32)
Left colon + rectum	5	1	3 (38)	33 (77)	0.039	21 (81)	13 (59)	NS	15 (60)	NS
Right + left colon	3	3	6 (75)	24 (56)	NS	13 (50)	16 (73)	NS	17 (68)	NS
TNM Stage					NS			NS		NS
I	0	1	1 (14)	2 (5)		2 (8)	0 (0)		1 (4)
II	1	0	2 (29)	23 (53)		16 (62)	9 (41)		9 (38)
III	4	3	4 (57)	15 (35)		7 (27)	11 (50)		12 (50)
IV	0	0	0 (0)	3 (7)		1 (4)	2 (9)		2 (8)
I/II	1	1	3 (43)	25 (58)	NS	18 (69)	9 (41)		10 (42)
III/IV	4	3	4 (57)	18 (42)		8 (31)	13 (59)	NS	14 (58)	0.050
Microsatellite instability					< 0.001			NS		0.038
MSI (MSI-L or MSI-H)	1	4	6 (75)	4 (9)		2 (8)	6 (27)		8 (32)
MSS (MSI-L or MSS)	5	0	2 (25)	39 (91)		24 (92)	16 (73)		17 (68)
Somatic mutations
TP53	6	0	3 (38)	25 (64)	NS	14 (61)	13 (62)	NS	14 (58)	NS
KRAS	1	2	2 (25)	14 (33)	NS	9 (35)	5 (23)	NS	7 (28)
BRAF	0	0	0 (0)	1 (2)		1 (4)	0 (5)		0 (0)
CTNNB1	0	0	0 (0)	1 (2)		0 (0)	1 (5)		1 (4)
Immunohistochemistry
Loss of MMR	1	4	5 (50)	5 (50)	NS	2 (8)	6 (27)	NS	8 (32)	0.038
Overexpression of p53	5	0	2 (25)	19 (44)	NS	9 (35)	11 (50)	NS	12 (48)	NS
Overexpression of MUC5AC	2	3	5 (63)	10 (23)	0.039	6 (23)	8 (36)	NS	9 (36)	NS

Ams: Extented Amsterdam II criteria; NS: Not statistically significant; Beth: Revised Bethesda Guidelines; MMR: Mismatch repair; CCR: Colorectal cancer; MSI: Microsatellite instability; MSS: Microsatellite stable; MUC: Mucin.

Table 3 Comparison of the somatic phenotype and genotype as a function of the patient’s clinical characteristics

	MSI (n = 10)	KRAS mutations (n = 16)	TP53 mutations (n = 28)	TP53 overexpression (n = 21)	MUC5AC overexpression (n = 15)
Mean age at diagnosis (range), yr	45 (18-72)	51.5 (18-85)	48.5 (18-79)	49.5 (24-75)	50 (24-76)
Sex
Males	80.00%	75.00%	57.10%	52.40%	66.70%
Females	20.00%	25.00%	42.90%	47.60%	33.30%
Tumor site1
Proximal	50.00%	18.80%	21.40%	28.60%	33.30%
Distal	50.00%	81.30%	78.60%	71.40%	66.70%
TNM stage2
I	10.00%	6.30%	0.00%	0.00%	0.00%
II	40.00%	43.80%	48.10%	38.10%	40.00%
III	50.00%	50.00%	44.40%	47.60%	53.30%
IV	0.00%	0.00%	7.40%	9.50%	6.70%

¹Proximal, right colon; distal, left colon + rectum;

²Tumor, node, metastasis (TNM) stage was unknown for one patient; MSI: Microsatellite instability; MUC: Mucin.

Table 4 Comparison of the microsatellite instability phenotype as a function of tumoral parameters

	MSI-H tumors (n = 10)	MSS tumors (n = 41)	P
MMR expression	100.00%	0.00%	< 0.00011
KRAS mutations	40.00%	29.30%	NS
TP53 mutations	30.00%	67.60%	NS
TP53 surexpression	10.00%	48.80%	0.03351
MUC5AC surexpression	70.00%	19.50%	0.00391

¹Fisher exact test. NS: Not significant; MSI: Microsatellite instability; MUC: Mucin; MMR: Mismatch repair; MSS: Microsatellite stable.

Table 5 Comparison of TP53 somatic mutations as a function of tumoral parameters

	Presence of TP53 mutations (n = 28)	Absence of TP53 mutations (n = 19)	P
MSI	10.70%	36.80%	NS
MMR expression loss	10.70%	36.80%	NS
KRAS mutations	25.00%	47.40%	NS
TP53 surexpression	60.70%	21.10%	0.00901
MUC5AC surexpression	21.40%	47.40%	NS

¹Fisher exact test. NS: Not significant; MSI: Microsatellite instability; MUC: Mucin; MMR: Mismatch repair.

Table 6 Comparison of mucin 5AC expression as a function of tumoral parameters

	MUC5AC expression (n = 15)	Absence of MUC5AC expression (n = 36)	P
MSI phenotype (n = 10)	46.70%	8.30%	0.00391
MMR expression loss (n = 10)	46.70%	8.30%	0.00391
TP53 mutations (n = 28)	40.00%	68.80%	NS
TP53 overexpression (n = 21)	33.30%	44.40%	NS
KRAS mutations (n = 16)	26.70%	33.30%	NS

¹Fisher exact test. NS: Not significant; MSI: Microsatellite instability; MUC: Mucin; MMR: Mismatch repair.

Table 7 Comparison KRAS somatic mutations as a function of tumoral parameters

	Presence of KRAS mutations (n = 16)	Absence of KRAS mutation (n = 35)	P
MSI	25.00%	17.10%	NS
MMR expression loss	25.00%	17.10%	NS
TP53 mutations	46.70%	65.60%	NS
TP53 overexpression	31.30%	45.70%	NS
MUC5AC overexpression	25.00%	31.40%	NS

NS: Not significant; MSI: Microsatellite instability; MUC: Mucin; MMR: Mismatch repair.