Incidence of DNA replication errors in patients with multiple primary cancers

Brown, S. R.; Finan, P. J.; Hall, N. R.; Bishop, D. Timothy

doi:10.1007/bf02236266

Cited by 33 publications

(23 citation statements)

References 17 publications

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“…The incidence of MSI-H in multiple cancerss (52%) is significantly higher than in single cancers (13.5%), consistent with other reports (Sengupta et al, 1997;Brown et al, 1998;Masubuchi et al, 1999;Pedroni et al, 1999;Yamashita et al, 2000). The presence of patients with HNPCC, known to be associated with MSI-H in 490% of cancers, might account for this.…”

Section: Discussionsupporting

confidence: 89%

“…Microsatellite instability has been reported in 33 -89% of cancers from patients with multiple cancers (Horii et al, 1994;Sengupta et al, 1997), including studies that excluded HNPCC clinically by the Amsterdam criteria (Brown et al, 1998;Masubuchi et al, 1999;Yamashita et al, 2000), although these results have been disputed (Pedroni et al, 1999). The Amsterdam criteria were not sufficiently selective (Beck et al, 1997), since the more rigorous Amsterdam criteria II (Vasen et al, 1999) and atypical HNPCC phenotypes associated with mutations in other MMR genes such as MSH6 (Wagner et al, 2001) were not considered.…”

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confidence: 99%

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The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers

et al. 2005

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There is increased incidence of microsatellite instability (MSI) in patients who develop multiple primary colorectal cancers (CRC), although the association with hereditary nonpolyposis colon cancer (HNPCC) is unclear. This study aims to evaluate the underlying genetic cause of MSI in these patients. Microsatellite instability was investigated in 111 paraffin-embedded CRCs obtained from 78 patients with metachronous and synchronous cancers, and a control group consisting of 74 cancers from patients with a single CRC. Tumours were classified as high level (MSI-H), low level (MSI-L) or stable (MSS). MLH1, MSH2 and MSH6 gene expression was measured by immunohistochemistry. Methylation of the MLH1 promoter region was evaluated in MSI-H cancers that failed to express MLH1, and mutational analysis performed in MSI-H samples that expressed MLH1, MSH2 and MSH6 proteins. The frequency of MSI-H was significantly greater in the multiple, 58 out of 111 (52%), compared to the single cancers, 10 out of 74 (13.5%), Po0.01. Of the 32 patients from whom two or more cancers were analysed, eight (25%) demonstrated MSI-H in both cancers, 13 (41%) demonstrated MSI-H in one cancer and 11 (34%) failed to demonstrate any MSI-H. MSI-H single cancers failed to express MLH1 or MSH2 in seven out of nine (78%) cases and MSI-L/MSS cancers failed to express MLH1 or MSH2 in one out of 45 (2.2%) cases, all cancers expressed MSH6. MSI-H multiple cancers failed to express MLH1 or MSH2 in 21 out of 43 (48%) cases and MSI-L/MSS cancers failed to express MLH1 or MSH2 in four out of 32 (12.5%) cases. MSH6 expression was lost in five MSI-H multiple cancers, four of which also failed to express MLH1 or MSH2. Loss of expression of the same mismatch repair (MMR) gene was identified in both cancers from six out of 19 (31%) patients. Methylation was identified in 11 out of 17 (65%) multiple and three out of six (50%) single MSI-H cancers that failed to express MLH1. Mutational analysis of 10 MSI-H multiple cancers that expressed MLH1, MSH2 and MSH6 failed to demonstrate mutations in the MLH1 or MSH2 genes. We suggest that, although MSI-H is more commonly identified in those with multiple colorectal cancers, this does not commonly arise from a classical HNPCC pathway.

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Section: Discussionsupporting

confidence: 89%

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confidence: 99%

The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers

et al. 2005

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“…As regards the pathogenesis of MPM of the digestive tract, it may be associated with multiple-spot cancerization and intracavitary implantation metastasis. The field cancerization theory presented by Slaughter et al (7) and Brown et al (8) may be a plausible explanation. Namely, mucosa covering a widespread area, rather than mucosal foci, is exposed to a carcinogen.…”

Section: Discussionmentioning

confidence: 92%

Synchronous multiple primary gallbladder and gastric malignancies: Report of two cases and review of the literature

Zhou

et al. 2017

mol clin onc

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Abstract. Multiple primary malignancies (MPM) are rare. In particular, synchronous gallbladder and gastric malignancies are extremely rare, are associated with a concealed onset and atypical symptoms, and are highly likely to be overlooked or misdiagnosed. The clinical data of two patients with synchronous gallbladder and gastric malignancies are herein reported and integrated with the relevant literature to retrospectively analyze and summarize the pathogenesis and clinical characteristics of MPM. Case 1 was a male 46-year-old patient who underwent laparoscopic cholecystectomy, and succumbed to extensive tumor metastasis 2 months after the operation. Case 2 was an 80-year-old female patient who was treated with distal gastrectomy for gastric cancer, cholecystectomy, gastrojejunostomy and dissection of 5 suprapyloric, 6 subpyloric, 7 left gastric and 8 common hepatic artery lymph nodes, and succumbed to multiple organ failure induced by extensive tumor invasion within 1 week after the operation. Clinical physicians must pay closer attention to early symptoms of MPM in order to make an accurate diagnosis, perform timely radical surgical treatment and achieve favorable therapeutic outcomes, in terms of significantly increasing long-term patient survival rates.

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“…Frequent MSI in multiple primary cancers of the colorectum or stomach have been reported (15,16). In one series (15), MSIϩ rate was reported in 17 (27.4%) of 62 cases of the multiple primary cancers excluding the HNPCC patients compared to 7 (8.1%) of 86 of the single primary colon cancers.…”

Section: Discussionmentioning

confidence: 99%

Microsatellite Instability in Double Primary Cancers of the Colorectum and Stomach

et al. 2001

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Incidence of DNA replication errors in patients with multiple primary cancers

Abstract: Results suggest that genetic instability plays an important role in development of multiple primary cancers, particularly from certain cancer subsets. Testing for replication errors may be an appropriate way of identifying individuals at risk of multiple primary cancers.

Cited by 33 publications

References 17 publications

The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers

The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers

Synchronous multiple primary gallbladder and gastric malignancies: Report of two cases and review of the literature

Microsatellite Instability in Double Primary Cancers of the Colorectum and Stomach

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