7.7 LU Redux
8.1.2 Permutations
46
Of the 117 cases only in 69 cases could the extent of the disease be assessed from clinical records, request cards and histology of tumour. The disease was classified as either advanced or localized on the bases of depth of tumour invasion on histology, presence of lymph node and/or other metastases. Based on this classification, about 92.8% (64/69) of patients presented with advance disease. The disease was only localized in 7.2% (5/69) of cases in which the tumour was histologically limited to the mucosa or the muscularis propria. There was no significant association between the depth of invasion of the tumour and the other clinicopathological features of the tumours.
Table 11: Frequency of tumour grades of Gastric Carcinoma diagnosed at the UCH, Ibadan between 2000 and 2011
Tumour grade Number of cases Frequency (%)
Well differentiated 54 46.2
Less differentiated 63 53.8
Total 117 100
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Table 12: Microsatellite Statuses of forty-seven gastric carcinoma samples using BAT25 and BAT26 loci
SAMPLE NO. BAT 25 BAT 26 SAMPLE NO. BAT 25 BAT 26 SAMPLE NO. BAT 25 BAT 26
1 MSS ND 18 MSS MSS 35 ND MSI
2 MSS ND 19 MSS MSS 36 MSS MSS
3 ND MSS 20 MSS MSS 37 ND MSS
4 MSS ND 21 MSS ND 38 ND MSS
5 MSS MSS 22 MSS ND 39 ND MSS
6 MSS ND 23 MSS ND 40 ND MSS
7 MSS MSS 24 MSI MSS 41 MSS MSS
8 MSS MSS 25 MSI ND 42 MSI ND
9 MSS MSS 26 MSS MSS 43 ND MSS
10 MSS MSI 27 MSS MSS 44 MSS ND
11 MSS ND 28 MSS ND 45 ND MSS
12 MSI ND 29 MSI ND 46 ND MSS
13 MSS ND 30 MSI MSS 47 ND MSS
14 MSS ND 31 MSS ND
15 MSI ND 32 MSI MSS
16 MSS MSS 33 MSI MSS
17 MSS MSI 34 MSS ND
MSS=microsatellite stable, MSI=microsatellite unstable, ND=not done.
None of the 18 cases tested showed concordance for MSI at both loci tested. However, 12/18 cases (66.67%) of gastric carcinoma cases showed concordance for MSS at both loci (Figure 10
&Table 12).
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The mean age of patients with MSI-positive tumours was 49.46+ 16.16, while that for patients with MSS tumours was 52.45+ 15.38. Table 13 below shows a summary of the relationship between the microsatellite status and the clinicopathological features of some gastric carcinoma diagnosed in Ibadan between 2000 and 2011. There was no significant difference between the mean ages of patients with MSI-positive and MSS tumours; just as no significant association was found between the anatomic site of tumour (p=0.188), patient’s gender (p=0.175), patient’s age group (0.772), gross morphology of tumour (0.148), histologic grade (p=0.129) or the histological type of tumour (p=0.423).
DLD1
SAMPLE 34
SAMPLE 19
SW 620
Figure 10: High Resolution Melt Curve result outputs showing Normalized Melt Curve and Difference Plot of microsatellite status of control (DLD1 and SW620) and test samples at BAT 25 locus. Sample 34 clustered with MSI- positive control DLD1, while sample 19 clustered with MSS control SW 620.
49
Table 13: Microsatellite status and clinicopathological features of gastric carcinoma
MICROSATELLITE STATUS
MSS MSI p value
ANATOMIC SITE OF TUMOUR
PYLORUS/ANTRUM 20 5 0.188
FUNDUS/CARDIA 0 1
UNKNOWN SITE 0 1
MULTIPLE SITES 1 0
GENDER MALE 22 10 0.175
FEMALE 13 2
GROSS
MORPHOLOGY
EXOPHYTIC 12 4 0.148
FLAT 6 0
ULCERO-INFILTRATIVE 4 3
AGE GROUP YOUNG 9 5 0.772
MIDDLE AGE 16 4
AGED 9 3
HISTOLOGICAL TYPE
INTESTINAL 15 8 0.423
DIFFUSE 15 3
MIXED 5 1
HISTOLOGIC GRADE
WELL DIFFERENTIATED 15 8 0.129
LESS DIFFERENTIATED 20 4
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CHAPTER SIX
DISCUSSION
6.1 CLINICOPATHOLOGICAL AND GENERAL FEATURES
The relative ratio frequency of 1.38% of gastric carcinoma found in this study is significantly lower than the figures of 2.73% and 3.6% obtained previously from the University College Hospital by Ogunbiyiin 2000.80 This reduction in frequency further supports the earlier assertion that there is a steady decline in the relative frequency of gastric carcinoma diagnosed in the Department of Pathology, UCH, Ibadan.3, 80 This decline may be due to increase in pathological diagnosis of tumour from other sites rather than an absolute decrease in the incidence of gastric carcinoma. This relative frequency also falls outside the national relative frequency range of 1.64% and 4.1% found in other studies across the country over three decades, although it is comparable to the 1.64% reported by Abdulkareem et al from Lagos in 2010.2-4, 33
A rate of 18.4% for gastric carcinoma relative to other gastrointestinal tumours is somewhat higher than the 12% that was reported obtained by Abdulkareem et al in Lagos in 2009. 4
In keeping with the fact that gastric carcinoma is a disease of predominantly middle age and the elderly, 77.4% of our cohort falls in the 45 years and above age group. Though the overall mean age of patients found in this study was 53.36 years and is similar to the result that had previously been reported in Ibadan and elsewhere the modal age group found in this study was the 51-60 years age group, a decade earlier than the 60-69 age group reported by Oluwasola from the same centre in 1998. 2, 4, 46, 47, 48 In absolute terms, however, this shift in modal age group in this study represents one patient difference between the 51-60 age range and the 61-70 years group.
Furthermore, when the patients were stratified into gender the modal age for male patients was
51
61-70 while that for the female was 51-60, even though there was no difference in the mean ages of the genders.
The modal age group found in this study is similar to what was reported in 2010 from three different centres (Lagos, Maiduguri and Ile-Ife).2, 33, 47 It however, contrasts with the peak age incidences of the 7th to 9th decades obtained in studies from Japan, China, Korea, Australia, the United Statesand the United Kingdom. 17, 31, 41, 42, 43, 44, 45 The male predominance of 1.72:1 found in this study concurs with the results of several other studies nationwide and worldwide.2,
3, 13, 17, 31, 33, 36, 41-44, 46-48
More than eighty per cent of gastric carcinomas in this study were distally located (pylorus/antrum). This preponderance of pyloric/ antral tumours was similarly reported by Oluwasola in Ibadan in 1998. In that study distally located tumours accounted for 83.2% of gastric carcinoma.48 Pyloric/antral predominance was also reported from Ife, Maiduguri, and in other parts of the world32, 33, 46, 47, 54, 55.
In consonance with the results of other studies, including a previous one from Ibadan, tumours from our patients exhibited predominantly an exophytic pattern of growth. Exophytic tumours make up about 62.3% of tumours found in this study, followed by the ulcero-infiltrative growth pattern (22.6%) and the flat/diffusely infiltrating (15.1%). 3, 13, 47, 48, 54, 55
The intestinal type of gastric carcinoma, similar to what was previously reported from Ibadan and other centres in Nigeria, was the commonest histological type of gastric carcinoma found in this study.2, 36, 47, 48 However, in contrast to the rate of 56-88.7% of intestinal type found in these previous studies, the present study found a lower rate of 47.0% rate for intestinal type tumour, 35.1% for diffuse and 17.9% for mixed/ indeterminate. The difference represents a rise in the
52
rate of the diffuse type of gastric carcinoma since the rate for the mixed/indeterminate has remained generally constant (17%-18.4%) over the past decade in Ibadan. This rise in the rate of the diffuse type of gastric carcinoma has similarly been reported in the United States over the past two decades and has been attributed to the relative fall in the intestinal type of gastric carcinoma globally.8, 20 The fall in the intestinal type of gastric carcinoma may be due to the widespread use of anti-H pylori treatment regimen for dyspeptic patients with chronic gastritis and peptic ulcer. This regimen has been shown to reverse precancerous lesion like chronic atrophic gastritis and intestinal metaplasia which are associated with H pylori infection.81
A significant association (p=0.002) was found between the macroscopic growth pattern and the histological morphology of the tumour. Intestinal and mixed/indeterminate tumours are more likely to exhibit the exophytic or ulcero-infiltrative growth pattern than tumours with diffuse histological morphology. Conversely, tumours with flat/ diffusely infiltrating gross morphology most probably have diffuse histological morphology than either exophytic or ulcero-infiltrative tumours. This association has not been previously reported in local studies, probably because it had not been sought for in these other studies, and deserves to be considered in future studies of gastric cancer from this environment.2, 3, 33, 47, 48
There was also a significant association between tumour grade and the gross morphology of tumour. The flat or diffusely infiltrating tumours tended to be less differentiated than exophytic/ulcero-infiltrative tumours, while well differentiated tumours are more likely to be exophytic/ulcero-infiltrative than flat. These associations have been classically described for gastric carcinoma. The better-differentiated gland-forming tumours typically form exophytic or ulcerated tumours, whereas, the poorly differentiated tumours composed mainly of discohesive cells, are diffusely infiltrating7, 8, 20.
53
C X 40 D X 100
X 40
A B X 100
B
E X 100 F X 400
Figure 11: Photomicrographs of intestinal (A & B), mixed (C & D) and diffuse (E & F) types of gastric carcinoma
54
Unlike the report by Abdulkareem et al from Lagos in 2010, and Zheng et al from Japan in 2007 where the diffuse histologic type of gastric carcinoma was significantly associated with the female gender, no association was found in this study between patients’ gender and the histological type of gastric carcinoma (p=0.056).2, 14 However, the most common histological type of tumour in the female patients was the diffuse type. Also, when the different histological types were re-grouped into well-differentiated (intestinal type) and less differentiated (diffuse and mixed) grades, the female gender was found to associate significantly with the less differentiated tumours (p=0.045). Perhaps, the use of a larger sample size may have been able to clarify true relationship between gender and the Lauren’s histological type of the tumour in our centre.
Furthermore, in contrast to the association between histologic type and the anatomic site (topography) of tumour reported by Oluwasola in UCH, Ibadan, in 1998, no such association was found in the present study (p=0.525).
Similar to the preponderance of advance stage of disease presentation that has been reported from several centres in Nigeria, this study found that 92.8% of cases presented in advanced stage.2, 3, 33, 47 This advanced stage presentation has also been reported from Western countries and Australia.8, 40, 48