Download the use of immunohistochemistry for diagnosis of colorectal cancer

RESEARCH PROPOSAL
TOPIC:
THE USE OF IMMUNOHISTOCHEMISTRY FOR
DIAGNOSIS OF COLORECTAL CANCER.
BY
OKEKE FIDELIS ODIRA
AREA OF SPECIALTY: HISTOPATHOLOGY
DEPARTMENT OF MEDICAL LABORATORY SCIENCE,
FACULTY OF HEALTH SCIENCES AND TECHNOLOGY,
NNAMDI AZIKIWE UNIVERSITY
INTRODUTION
Colorectal cancer is an important public health problem; it stands at the top of oncologic
pathology, in Romania and in the world. It is a disease in which abnormal cells in the
colon or rectum divide uncontrollably, ultimately forming a malignant tumour. The colon
and rectum are part of the large intestine which is the lower part of the body’s digestive
system, which takes up nutrients from food and water and stores solid waste until it passes
out of the body. These cancers can also be referred to separately as colon cancer or rectal
cancer depending on where they first start. It is common in both men and women.
Colorectal cancer is a major cause of cancer mortality and morbidity worldwide,
representing 8.9% of all cancers (Afify et al., 2008). Colorectal cancer is the third most
common type of non-skin cancer in both men (after prostate cancer and lung cancer) and
women (after breast cancer and lung cancer), and the second leading cause of cancer death
in United Kingdom and United States after lung cancer (Siegel et al., 2011, Strimpakos et
al., 2009). It is estimated that a total of 136,830 people in the United States will be
diagnosed with colorectal cancer and 50,310 people will die from it in 2014 (American
Cancer Society, 2014).
The rates of new colorectal cancer cases and deaths among adults aged 50 years or older
are decreasing in this country. However, the incidence is increasing among young adults.
In a cancer pathology registry done by National Cancer Institute, Cairo University,
colorectal cancer (CRC) had a relative frequency of 5% of the total estimated cancers and
29% of gastrointestinal malignancies with male predominance ratio of 3:1. According to
the study of 427 cases, more than 1/3 of cases were under the age of 45 (early onset) with
large tumor size at presentation (Mokhtar et al., 2007).
Despite continuing advances in therapeutic strategies, recurrence rates of colorectal cancer
are still high, with more prevalence in rectal rather than colon cancer with ratios of 33%
and19%, respectively (Tamer and Taha, 2012). Distant metastasis is the main cause of
death in colorectal patients and surgical resection remains the only potentially curative
option for patients with metastatic colorectal cancer. However, curative resection is
possible in <25% of patients with stage IV disease (Cejas et al., 2009).
More than 90% of colorectal carcinomas are adenocarcinomas originating from epithelial
cells of the colorectal mucosa (Hamilton et al., 2010). It often begins as a growth called
polyp, which may form on the inner wall of the colon or rectum. Although the risk factors
for colorectal cancer are family history and older age, several other risk factors have been
associated with increased risk, including excessive alcohol use, obesity, being physically
inactive, cigarette smoking, and possibly, diet.
In addition, people with a history of inflammatory bowel disease (such as ulcerative colitis
or Crohn’s disease) have a higher risk of colorectal cancer than people without such
conditions. And people who have a family history of colorectal cancer or certain inherited
conditions (such as Lynch syndrome and familial adenomatous polyposis) also have an
increased risk of colorectal cancer and several other types of cancers, including
endometrial, ovarian, stomach, and urinary tract cancers (Hendriks et al., 2006, Umar et
al., 2004).
Immunohistochemistry plays an important role in differentiating tumour types, assessment
of aggressiveness and recognizing of metastasis origin. Many immunohistochemical
studies have investigated the relationship between immunohistochemical characteristics
and
histopathological
immunohistochemical
findings
studies
in
is
colorectal
to
detect
tumors.
An
cancer
in
important
early
immunohistochemical testing helps find out cancers in their earliest stage.
goal
stages,
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Justification of Study
The recent alarm on the rising incidence of cancer by the World Health Organisation
(WHO) should be a thing of worry. About 7.6 million persons died of cancer in 2008
worldwide and there is indication that the figure could escalate to 13 million by the year
2030.
The study of colorectal cancer is a main preoccupation for the researchers
worldwide due to the high incidence of the disease. The insidious onset and the deficiency
of national population screening programs are the main underlying causes of colorectal
cancer to be diagnosed in an advanced stage when treatment possibilities are limited and
the chances for survival very low, the result being increased morbidity and mortality from
colorectal cancer as seen in many countries, both European and worldwide. This has
formed the basis for choosing the topic; the use of immunohistochemistry in diagnosis of
colorectal cancer.
Aims and Objectives
1. To analyze the colon and rectal samples for features suggestive of colorectal
carcinoma.
2. To evaluate colorectal precursor protein expression using immunohistochemical
stains.
3. To identify correlations between immunohistochemical aspects and the prognosis
of patients with colon cancer.
4. To assess the feasibility of using immunohistochemistry to detect replication error
positivity of colorectal cancer.
5. To determine the frequency and variations of colorectal lesion within patients
subgroup
6. To provide a baseline data that will aid in screening of patients and combating
colorectal cancer menace.
MATERRIALS AND METHODS
Data and Tissue Collection.
Paraffin embedded tissue samples from 800 colorectal cancer patients with or without liver
metastasis will be collected from the archive of Histopathology Laboratory of Nnamdi
Azikiwe University Teaching Hospital, Nnewi to be used for the study.
The
clinicopathological data including age, sex, microscopic types, histological grade and
lymph node status will be collected for statistical analysis.
Ethical Approval
Ethical approval will be sought for and obtained from the ethical committee of NAUTH,
Nnewi.
Stains and Techniques
Triplicate sections (4µm) each will be cut from all the samples and stained using
haematoxylin and eosin stain to determine the histological diagnosis for selecting positive
tissues for immunohistochemical studies using the required antigens.
Statistical Analysis
Data will be presented as percentages and the mean ± standard deviation. It will be
analyzed using one way analysis of variance (ANOVA) and student’s t-test. P-values of
<0.05 will be considered significant, using IBM SPSS version 15.0
REFERENCES
Afify M, Samy N, Hashim M, Essam T (2008). Clinical significance of vascular
endothelial
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American Cancer Society (2014). Colorectal Cancer Facts & Figures 2014 - 2016.
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(2009). K-RAS mutations in primary colorectal cancer tumors and
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Hamilton SR, Bosman FT, Boffetta P, et al (2010). Carcinoma of the colon and rectum. In:
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Hendriks, Y. M., de Jong, A. E., Morreau, H., Tops, C. M., Vasen, H. F., Wijnen, J. T., et
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