Table 3.

Clinical and morphological comparison of LS and FCCTX [14, 15, 23-33].

__		FCCTX		LS			P-value, OR1 and RR2		References
Location		Predominantly distal location of tumour in sigmoideum and/or rectum (left colon and/or rectum)		Predominantly location of tumour proximal for the splenic flexure (right colon)			<0.0001 0.15 0.010 0.001 Not given 0.00001 0.001 Not given		Klarskov et al. [27] Llor et al. [26] Mueller Koch et al. [28] Valle et al. [29] Francisco et al. [32] Dominguez-Valentin et al. [30] Shiovitz et al. [31] Benatti et al. [25]
Mean age-of-onset of CRC		60.7 years 51 years 54 years 63.4 years 60.2 years 60 years 55 years 53 years 58 years 53.3 years		48.7 years 46/45 years3 44 years 47.6/49 years4 53.8 years 54 years 41 years 41 years 53 years 50.5 years			Not given 0.001 Not given <0.05 0.0.036 0.01 <0.001 <0.001 Not given OR1= 1.02 CI5: 1.00-1.03		Lindor et al. [14] Russo et al. [23] Dove-Edwin et al. [24] Benatti et al. [25] Llor et al. [26] Klarskov et al. [27] Mueller Koch et al. [28] Valle et al. [29] Dominguez-Valentin et al. [30] Shiovitz et al. [31]
CRC risk		2.3 (SIR6) Lower than LS		6.1 (SIR6) Higher than FCCTX			< 0.001 RR2 = 2.08, CI5: 1.16-3.73		Lindor et al. [14] Benatti et al. [25]
Risk for developing extra-colonic cancers		Lower than LS		Higher than FCCTX			Not given 0.025 <0.001 RR2 = 7.59, CI5: 1.71-33.7		Lindor et al. [14]7 Mueller Koch et al. [28] Valle et al. [29]8 Benatti et al. [25]9
Incidence of extracolonic HNPCC-related cancer		6.4% 3.3%		25%/18.2%4 5.1%			0.03 Not given		Benatti et al. [25]9 Llor et al. [26]10
Differentiation		High differentiation		Poor differentiation			<0.0001 0.09111 Not given 0.00001 OR1 = 0.33, CI5: 0.14-0.7812		Klarskov et al. [27] Llor et al. [26] Francisco et al. [32] Dominguez-Valentin et al. [30] Shiovitz et al. [31]
Carcinoma subtype and architecture		More heterogeneous architecture, compared to LS with a high frequency of tubular architecture		Less heterogeneous architecture than FCCTX with a high frequency of mucinous and solid architecture			0.02, 0.02, 0.0003. 0.000113		Klarskov et al. [27]
Mucin production		Low frequency of mucin production		High frequency of mucin production			0.01, 0.00114 0.50211 0.03 Not given		Klarskov et al. [27] Llor et al. [26] Valle et al. [29] Francisco et al. [32]
Dirty necrosis		High degree of dirty necrosis		Absence of dirty necrosis			<0.0001		Klarskov et al. [27]
Peritumorous lymphocytes		Lower rate of peritumorous lymphocytes than LS		Higher rate of peritumorous lymphocytes than FCCTX			0.02 OR1 = 0.49, CI5: 0.26-0.90		Klarskov et al. [27] Shiovitz et al. [31]
Tumour-infiltrating lymphocytes		Low rate of tumour-infiltrating lymphocytes		High rate of tumour-infiltrating lymphocytes			<0.0001 0.033 Not given OR1 = 0.14, CI5: 0.07-0.26		Klarskov et al. [27] Llor et al. [26] Francisco et al. [32] Shiovitz et al. [31]
__	FCCTX		LS		P-value, OR1 and RR2	References
Crohn-like reactions	Low degree of Crohn-like reactions		High degree of Crohn-like reactions		0.003 OR1 = 0.27, CI5: 0.14-0.54	Klarskov et al. [27] Shiovitz et al. [31]
Synchronous and metachronous tumours	Low rate of synchronous and metachronous tumours		More synchronous and metachronous colorectal tumours compared to FCCTX		0.017, <0.00115 Not given	Mueller Koch et al. [28] Francisco et al. [32]
Tumour budding	High degree of tumour budding		Low degree of tumour budding		<0.000116	Klarskov et al. [27]
Adenoma/ carcinoma ratio	Higher adenoma/carcinoma ratio compared to LS		Lower adenoma/carcinoma ratio compared to FCCTX		0.03 Not given	Mueller Koch et al. [28] Francisco et al. [32]
Invasive border	Infiltrative growth pattern		Expansive growth pattern		<0.000117	Klarskov et al. [27]
Chromosomal stability	High degree of gains and losses (CIN+18) with frequently gain of 20q and loss of 18		Generally chromosomal stable (CIN-)		<0.0119 Not given	Therkildsen et al. [33] Abdel Rahman et al. [15]

¹ Odds ratio; 2 Risk ratio; 3 MLH1 mutation positive and MSH2 mutation positive respectively; 4 HNPCC MSI MLH1/MSH2 mutation positive and HNPCC MSI MLH1/MSH2 mutation negative respectively; ⁵ Confidence Interval; ⁶ Standardized Incidence Ratio; ⁷ Extracolonic HNPCC-related cancer. Defined as cancer in uterus, ventricle, kidney, ovary, small intestine, ureter; ⁸ HNPCC-related cancer, not defined; ⁹ Extracolonic HNPCC-related cancer. Defined as cancer in endometrium, stomach, renal pelvis, ureter, ovary; ¹⁰ All endometrial cancer; ¹¹ Not significant; ¹² OR for FCCTX vs. LS tumours being poorly differentiated; ¹³ P-values for FCCTX tumours showing more heterogeneous architecture than LS, higher frequency of tubular pattern in FCCTX and higher frequency of solid and mucinous morphologies in LS, respectively; ¹⁴ P-values for intracellular and extracellular mucin, respectively; ¹⁵ P-value for CRC and extracolorectal tumours respectively; ¹⁶ P-value <0.0001 is given in Table 2, while p-value 0.1 is given in the text. The p-value <0.0001 includes uncertain cases, while the p-value 0.1 comprises definite cases, only (personal communication); ¹⁷ P-value for FCCTX more often displaying infiltrative growth compared to LS; ¹⁸ Chromosomal instability positive; ¹⁹ P-value for 20q gain and 18 loss