Hyperplastic Polyposis Study (HPP)
Principal Investigator: Prof. Jeremy
R. Jass
Department of Pathology
McGill University, Duff Medical Building
3775 University Street
Montreal, Quebec H3A 2B4 Canada
e-mail: jeremy.jass@mcgill.ca
Background:
There is growing awareness that the condition hyperplastic polyposis (HPP) is precancerous. The management of HPP remains problematic with little evidence to guide decisions relating to surveillance or surgical intervention.
Aim
The aim of the study is to identify features (clinical, pathological, molecular) that are predictive of colorectal cancer in HPP.
Methods
Patients meeting the definition of HPP (see protocol) will be registered through the completion of a simple questionnaire that will gather demographic data and clinicopathological features such as type, size, number and distribution of polyps. The patients may either have an intact colon or have had a previous colectomy to facilitate the management of large numbers of polyps and/or treat cancer. Histological sections will be examined by a panel of pathologists to score additional histological features of polyps. Immuno-histochemical and molecular studies on tissue blocks will be performed. The prospective collection of fresh samples would be desirable as a prospective arm of the study.
Analysis
Univariate and multivariate analysis will be undertaken to identify variables that are linked with colorectal cancer or the presence of high-grade dysplasia amounting to carcinoma-in situ. Using the features that provide an independent association with colorectal cancer models will be developed that will stratify patients into low, intermediate and high-risk groups.
Outcome
This evidence obtained through this study should help to guide the management of patients with HPP including the determination of surveillance intervals and the extent of surgery in subjects with colorectal cancer.
PROTOCOL DETAILS
Step 1
This is to achieve an agreed definition of hyperplastic polyposis. For the purposes of this study the following working definition based on that proposed by Burt and Jass will be employed:
Definition of hyperplastic polyposis (HPP):
1. 20 HPs* and/or
2. 5 HPs if two are at least 1cm in size and/or
3. Any number of HPs in subject with 1st degree relative with HPP
Caveats:
A. Exclude all distal HPs from count (within 20 cm of anal verge –
measurement obtained either from surgical specimen or on withdrawal of
colonoscope)
B. Include other types of serrated polyp in count (e.g. serrated adenoma
and mixed polyp)
C. Total polyp count can accumulate over time
Step 2:
Completion of questionnaire for registration and data entry.
See separate questionnaire
Step 3:
Histology review of polyps by panel of pathologists (not all cases enrolled in this study have to be accompanied by slides for review).
The aim of the histology review is three-fold: (1) to establish and refine diagnostic criteria for different types of polyp, (2) to establish reasons for inter-observer disagreement and thereby improve diagnostic reliability, and (3) to determine if particular histological features may be predictive of cancer risk. This part of the study will also require the development of a data entry form for participating pathologists.
Step 4:
Undertake immuno-histochemical studies on polyps, for example markers of proliferation, apoptosis, differentiation and DNA repair (MGMT and MLH1). This will require the provision of either unstained slides or blocks.
Step 5:
Undertake molecular studies of polyps, for example mutation of KRAS and BRAF and DNA methylation. This will require the provision of blocks or extracted DNA.
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