WEEK 3: Cancer in the GI tract

Question 1

8 A 70-year-old man with a lengthy history of chronic
alcoholism has had increasing difficulty of swallowing and has noticed a 6-kg weight loss over the past 2 months.
On physical examination, there are no remarkable findings.

Upper gastrointestinal endoscopy shows a 3-cm ulcerative
mass in the mid-esophagus that partially occludes the
esophageal lumen. Esophagectomy is performed, the gross
appearance of the lesion is shown in the figure.

Which of the following is most likely to be seen on
microscopic section of this mass?
 (A) Multinucleated cells with intranuclear inclusions
 (B) Squamous cell carcinoma
 (C) Dense collagenous scar
 (D) Adenocarcinoma
 (E) Thrombosed vascular channels

Answer 1

A: (B) Squamous cell carcinoma

Explanation:

Multinucleated cells with intranuclear inclusions: This option suggests a viral infection such as herpes simplex virus, which is unlikely given the context of a chronic condition and ulcerative mass.

Squamous cell carcinoma: Chronic alcoholism significantly increases the risk of squamous cell carcinoma of the esophagus, particularly in the mid-esophagus. The ulcerative nature of the mass also supports this diagnosis.

Dense collagenous scar: This could be seen in a healed ulcer, but it does not account for the progressive symptoms and significant weight loss.

Adenocarcinoma: More commonly found in the lower esophagus and associated with Barrett’s esophagus and gastroesophageal reflux disease (GERD), rather than chronic alcoholism alone.

Thrombosed vascular channels: This is not typically associated with esophageal cancer and does not explain the clinical presentation.

Question 2

State the two major histological subtypes of esophageal cancer.

Answer 2

 Esophageal squamous cell carcinoma (ESCC)
 Esophageal adenocarcinoma (EAC).

Question 3

Q: Which subtype of esophageal cancer is more common worldwide?

Q: Which subtype of esophageal cancer is increasing in prevalence in the United States and other Western countries?

Answer 3

A: Esophageal Squamous Cell Carcinoma (ESCC) is more common worldwide.

A: Esophageal Adenocarcinoma (EAC) is increasing in prevalence in the United States and other Western countries.

Question 4

Q: What are the two major risk factors for Esophageal Squamous Cell Carcinoma (ESCC)?

Q: What other factors may increase the risk of Esophageal Squamous Cell Carcinoma (ESCC)?

Answer 4

A: The two major risk factors for Esophageal Squamous Cell Carcinoma (ESCC) are tobacco smoking and alcohol consumption.

A: Other factors that may increase the risk of Esophageal Squamous Cell Carcinoma (ESCC) include the consumption of hot beverages, nutritional deficiency, and exposure to environmental toxins.

Question 5

Q: Is the role of human papillomavirus (HPV) infection in increasing the risk of Esophageal Squamous Cell Carcinoma (ESCC) well established?

Q: Is the molecular pathogenesis of Esophageal Squamous Cell Carcinoma (ESCC) well understood?

Answer 5

A: No, the role of human papillomavirus (HPV) infection in increasing the risk of Esophageal Squamous Cell Carcinoma (ESCC) is still under debate.

A: No, the molecular pathogenesis of Esophageal Squamous Cell Carcinoma (ESCC) remains incompletely defined.

Question 6

Q: What is the primary precursor condition for esophageal adenocarcinoma (EAC)?

Q: How does Barrett esophagus typically develop?

Answer 6

A: Barrett esophagus is the primary precursor condition for EAC.

A: Barrett esophagus typically develops as a complication of gastroesophageal reflux disease (GERD), leading to a columnar metaplasia of the lower esophageal mucosa.

Question 7

Q: What are some of the risk factors associated with EAC?

Q: Describe the sequence of development leading to EAC.

Answer 7

A: Risk factors for EAC include gastroesophageal reflux disease (GERD), cigarette smoking, and obesity.

A: EAC develops through a sequence involving chronic exposure to gastroesophageal reflux, leading to the development of Barrett esophagus. Over time, dysplasia may occur within Barrett esophagus, progressing to adenocarcinoma.

Question 8

Define Barett’s esophagus.

Describe the pathogenesis of Barrett’s esophagus.

Answer 8

Definition: intestinal metaplasia of the esophageal mucosa induced by chronic reflux.
*Columnar epithelium instead of the normal squamous epithelium.
*A premalignant change

Pathophysiology
Reflux esophagitis → stomach acid damages mucosa of distal esophagus → nonkeratinized stratified squamous epithelium is replaced by non-ciliated columnar epithelium and goblet cells (intestinal metaplasia, Barrett metaplasia)

Question 9

Q: What is the proposed pathogenesis of esophageal adenocarcinoma (EAC)?

Q: What are some of the early molecular changes associated with the development of EAC?

Q: What genetic alterations are observed later during the progression of EAC?

Answer 9

A: The progression of Barrett esophagus to adenocarcinoma is suggested to occur over an extended period through the stepwise acquisition of genetic and epigenetic changes.

A: Early molecular changes include chromosomal abnormalities, mutation of TP53, and downregulation of the cyclin-dependent kinase inhibitor CDKN2A (p16/INK4a).

A: Later in progression, there is observed amplification of genes such as EGFR, ERBB2, MET, cyclin D1, and cyclin E.

Question 10

Morphology of Squamous cell carcinoma.

Q: What is the common site for squamous cell carcinoma of the esophagus?

Q: How does squamous cell carcinoma typically present in its early stages?

Answer 10

A: Squamous cell carcinoma of the esophagus commonly occurs in the middle third of the esophagus.

A: In its early stages, squamous cell carcinoma may appear as small, grey-white, plaque-like thickenings.

These lesions can be referred to as in situ lesions, squamous dysplasia, intraepithelial neoplasia, or carcinoma in situ.

Question 11

Q: What are the characteristics of symptomatic lesions of squamous cell carcinoma?

Q: How does squamous cell carcinoma spread and what are its effects on the esophageal wall?

Answer 11

A: Symptomatic lesions of squamous cell carcinoma may be polypoid, exophytic, and protrude into and obstruct the esophageal lumen. Some patients may also present with ulceration.

A: Squamous cell carcinoma typically spreads diffusely within the esophageal wall, causing thickening, rigidity, and luminal narrowing.

Question 12

Morphology of Esophageal adenocarcinoma

Q: Where does esophageal adenocarcinoma typically occur within the esophagus?

Q: How does esophageal adenocarcinoma initially appear?

Answer 12

A: Esophageal adenocarcinoma usually occurs in the distal third of the esophagus and may invade the adjacent gastric cardia.

A: Initially, esophageal adenocarcinoma may appear as flat or raised patches within otherwise intact mucosa.

Question 13

Q: What are some characteristics of advanced esophageal adenocarcinoma?

Q: What type of structures do tumors in esophageal adenocarcinoma commonly produce?

Answer 13

A: In advanced stages, large masses of 5 cm or more in diameter may develop. Alternatively, tumors may infiltrate diffusely or ulcerate and invade deeply.

A: Tumors in esophageal adenocarcinoma commonly produce mucin and form glands.

Question 14

Q: How does the lymphatic network contribute to the spread of esophageal squamous cell carcinoma (ESCC)?

Answer 14

A: The rich submucosal lymphatic network in the esophagus promotes both circumferential and longitudinal spread of ESCC.

Intramural tumor nodules may also be present several centimeters away from the main mass, contributing to further dissemination.

Question 15

Q: What is a common problem associated with esophageal carcinoma besides the cancer itself?

Answer 15

A: Malnutrition due to swallowing difficulty is another significant problem associated with esophageal carcinoma. Difficulty in swallowing, often caused by the tumor obstructing the esophageal lumen, can lead to decreased food intake and subsequent malnutrition.

Question 16

Q: What are some common presenting symptoms of esophageal carcinoma?

Q: What are some consequences of esophageal carcinoma on the patient’s health?

Answer 16

A: Esophageal carcinoma commonly presents with symptoms such as dysphagia (difficulty swallowing), odynophagia (pain on swallowing), or obstruction.

A: Esophageal carcinoma can lead to prominent weight loss and debilitation (los of strength or vitality) primarily due to impaired nutrition from swallowing difficulties and the effects of the tumor itself.

Question 16

Q: What complications may arise from esophageal carcinoma?

Q: What is the 5-year survival rate for individuals with superficial esophageal squamous cell carcinoma?

Answer 16

A: Hemorrhage and sepsis may accompany tumor ulceration, and symptoms of iron deficiency are often present.

A: The 5-year survival rate for individuals with superficial esophageal squamous cell carcinoma is reported to be 75%.

Question 17

Q: How aggressive is esophageal cancer?

Q: Which countries have a particularly high prevalence rate of esophageal cancer?

Answer 17

A: Esophageal cancer is considered an extremely aggressive cancer with one of the highest mortality rates among cancers.

A: China and South Africa are two countries with a very high prevalence rate of esophageal cancer.

Question 18

A 53-year-old woman has had nausea, vomiting, and mid epigastric pain for 5 months.
On physical examination, there are no significant findings.

 An upper gastrointestinal radiographic series shows gastric outlet obstruction.
 Upper gastrointestinal endoscopy shows an ulcerated mass that is 2 × 4 cm at the pylorus.

Which of the following neoplasms is most likely to be seen in a biopsy specimen of this mass?
 (A) non-Hodgkin lymphoma
 (B) Neuroendocrine carcinoma
 (C) Squamous cell carcinoma
 (D) Adenocarcinoma
 (E) Leiomyosarcoma

Answer 18

(D) Adenocarcinoma

Esophageal adenocarcinoma commonly presents with symptoms such as nausea, vomiting, and epigastric pain, and it can cause gastric outlet obstruction when located near the pylorus. The description of an ulcerated mass at the pylorus aligns with the typical presentation of adenocarcinoma in this scenario.

Question 19

Q: What is the most common type of malignancy in the stomach?

Answer 19

A: Gastric Adenocarcinoma is the most common malignancy of the stomach, accounting for more than 90% of all gastric cancers.

Question 20

Q: How is gastric adenocarcinoma often morphologically categorized?

Answer 20

A: Gastric adenocarcinoma is often morphologically categorized into two types: intestinal type and diffuse type.

Question 21

Q: What are some risk factors associated with gastric cancer?

Answer 21

A: Gastric cancer is more common in lower socioeconomic groups and in individuals with multifocal mucosal atrophy and intestinal metaplasia.

These factors are often associated with chronic inflammation, such as that caused by Helicobacter pylori infection, and dietary factors.

A: Some important risk factors for gastric adenocarcinoma include chronic gastritis, with Helicobacter pylori infection being the most common cause, as well as autoimmune gastritis.

Other risk factors include exposure to N-nitroso compounds and benzo[a] pyrene, the use of salt and smoking for food preservation, and mutations in the tumor suppressor gene CDH1, which encodes the cell adhesion protein E-cadherin.

Question 22

Q: How does chronic gastritis predispose to gastric adenocarcinoma?

Answer 22

A: Chronic gastritis predisposes to gastric adenocarcinoma by promoting gastric epithelial dysplasia. Gastric dysplasia and adenomas are recognizable precursor lesions to gastric adenocarcinoma.

Question 23

Q: Is gastric cancer predominantly hereditary?

Answer 23

A: No, the majority of gastric cancers are not hereditary. While mutations in certain genes like CDH1 can increase the risk, most cases of gastric cancer are associated with environmental factors such as H. pylori infection and dietary habits.

Question 24

Q: What are the typical locations for gastric adenocarcinoma?

Q: How are gastric adenocarcinomas classified based on histologic morphology?

Answer 24

A: Gastric adenocarcinoma is typically found in the antrum and the lesser curvature of the stomach more often than the greater curvature.

A: Gastric adenocarcinomas are classified into two subtypes based on histologic morphology: intestinal and gastric/diffuse type.

Question 25

Q: Describe the morphology of intestinal-type gastric adenocarcinoma.

Answer 25

A: Intestinal-type gastric adenocarcinomas tend to form bulky tumors composed of glandular structures.

Question 26

Q: Describe the morphology of gastric/diffuse-type gastric adenocarcinoma.

Answer 26

A: Gastric/diffuse-type gastric adenocarcinomas exhibit an infiltrative growth pattern and are more often composed of signet-ring cells.

Question 27

Q: What is the characteristic appearance of diffuse-type gastric adenocarcinoma?

Answer 27

A: The diffuse type infiltrates the gastric wall diffusely, flattens the rugal folds, and makes the gastric wall rigid and thickened, imparting a leather bottle appearance termed linitis plastica.

Question 28

Q: What is the status of metastases typically at the time of diagnosis of gastric adenocarcinoma?

Answer 28

A: Metastases are often detected at the time of diagnosis of gastric adenocarcinoma.

Question 29

Q: What are some common sites of metastases in gastric adenocarcinoma?

Answer 29

A: Common sites of metastases in gastric adenocarcinoma include:

*The supraclavicular sentinel lymph node (Virchow node)
*Periumbilical lymph nodes (Sister Mary Joseph nodule)
*The left axillary lymph node (Irish node)
*The ovary (Kruckenberg tumor)
*The pouch of Douglas (Blumer shelf)

Additionally, metastases can occur to other organs such as the liver, pancreas, duodenum, and spleen.

Question 30

Q: What are some characteristics of the clinical features of gastric adenocarcinoma?

Q: How does diffuse gastric cancer differ from other types of gastric adenocarcinoma?

Answer 30

A: Clinical features of gastric adenocarcinoma are non-specific, making diagnosis challenging. The mean age of presentation is around 55 years, and there is a male-to-female ratio of 2:1.

A: Diffuse gastric cancer is relatively uniform across countries, lacks identified precursor lesions, and occurs at similar frequencies in males and females.

Question 31

Q: What are the most powerful prognostic indicators in gastric cancer?

Q: What is the 5-year survival rate for early gastric cancer with surgical resection?

Q: How does the 5-year survival rate for advanced gastric cancer compared to early gastric cancer?

Answer 31

A: The depth of invasion and the extent of nodal and distant metastases at the time of diagnosis are the most powerful prognostic indicators in gastric cancer.

A: With surgical resection, the 5-year survival rate of early gastric cancer can exceed 90%, even if lymph node metastases are present.

A: In contrast, the 5-year survival rate for advanced gastric cancer remains less than 20%.

Question 32

Q: What percentage of gastric malignancies are primary lymphomas, and which type is most common?

Q: What are lymphomas of mucosa-associated lymphoid tissue (MALT) commonly referred to as?

Answer 32

: Nearly 5% of all gastric malignancies are primary lymphomas, with the most common type being indolent extra nodal marginal zone B-cell lymphomas.

A: Lymphomas of mucosa-associated lymphoid tissue (MALT) are commonly referred to as MALTomas.

Question 33

Q: Describe the pathogenesis of extra nodal marginal zone B-cell lymphomas.

Q: What can MALTomas transform into, and what is the significance of this transformation?

Answer 33

A: Extranodal marginal zone B-cell lymphomas usually arise at sites of chronic inflammation. MALT is typically induced as a result of chronic gastritis caused by Helicobacter pylori infection.

A: MALTomas can transform into more aggressive tumors that are histologically identical to diffuse large B-cell lymphomas.

This transformation is significant because diffuse large B-cell lymphomas are not responsive to H. pylori eradication, making them more challenging to treat

Question 34

A 38-year-old man who has been HIV positive for 10 years
has had severe nausea and vomiting for the past 2 weeks.
 On physical examination, he is afebrile. A stool sample is
positive for occult blood.
 The abdomen is not distended, there are no palpable
masses or organomegaly, and bowel sounds are present.
The patient has oral thrush.
 There are several reddish purple, 0.5- to 1-cm nodules on
the skin of the trunk. Laboratory studies show a CD4+
lymphocyte count of 118/μL.
 Upper gastrointestinal endoscopy shows 12 reddish purple,
0.6- to 1.8-cm, gastric mucosal nodules.
 A biopsy specimen of the nodules is most likely to show
which of the following neoplasms?
 (A) Adenocarcinoma
 (B) Non-Hodgkin lymphoma
 (C) Carcinoid tumor
 (D) Gastrointestinal stromal tumor
 (E) Kaposi sarcoma
 (F) Peutz-Jeghers polyp
 (G) Squamous cell carcinoma
 (H) Tubular adenoma

Answer 34

(E) Kaposi sarcoma, non-Hodgkin lymphoma, and anorectal squamous carcinoma are the only neoplasms listed that define AIDS in patients with HIV infection.

 Kaposi sarcoma most often involves the skin, but it can be found anywhere in the body, including the gastrointestinal tract.
 Kaposi sarcoma is a vascular lesion—hence the blue colour.
 Non-Hodgkin lymphomas and squamous carcinomas have a white cut surface and rarely are large enough to cause obstruction.
 Adenocarcinoma of the stomach can produce a mass, or it can diffusely infiltrate the gastric wall.
 Carcinoid tumors can be multiple, but they are most common in the small and large bowel or appendix and have a yellowish appearance.
 Gastrointestinal stromal tumors are rare and are typically large masses that have a white cut surface.
 Peutz-Jeghers polyps are associated with mucocutaneous pigmentation.
 Tubular adenomas (adenomatous polyps) are most common in the colon in older adults.

Question 35

7 A 70-year-old man saw his physician for a routine health
maintenance examination. On physical examination, there
were no remarkable findings, but a stool sample was positive for occult blood.
 A colonoscopy was performed and showed a 5-cm sessile
mass in the upper portion of the descending colon at 50 cm
from the anal verge. The gross picture shown on the left.
 The histologic appearance at low power of a biopsy specimen of the lesion is shown in the figure. The patient refused further work-up and treatment.
 Five years later, he sees his physician because of
constipation, microcytic anemia, and a 5-kg weight loss over
the past 6 months.
 What was the tumour this patient was having before 5 years?
Which is the tumour now?
 (A) Adenocarcinoma
 (B) Non-Hodgkin lymphoma
 (C) Carcinoid tumor
(D) Leiomyosarcoma
(E) Mucinous cystadenoma
(F) Squamous cell carcinoma
(G) tubiloVillous adenoma

Answer 35

The patient’s initial findings, including a 5-cm sessile mass in the colon that was positive for occult blood and showed a specific histologic appearance, along with the progression to symptoms such as constipation, microcytic anemia, and significant weight loss, strongly suggest a progression from a precancerous lesion to a malignancy.

Given the initial description and the histologic features typically associated with these types of lesions in the colon, the most likely diagnosis is:

Initial tumor (5 years ago):
(G) Tubulovillous adenoma

Current tumor (now):
(A) Adenocarcinoma

Tubulovillous adenomas are known precursors to colorectal adenocarcinomas, especially when left untreated over several years. The patient’s refusal of further work-up and treatment likely allowed the adenoma to progress to an invasive adenocarcinoma, which explains the current symptoms of constipation, anemia, and weight loss.

Question 36

Q: What is the most common malignancy of the gastrointestinal tract?

Q: At what age does the incidence of colorectal cancer (CRC) peak, and what percentage of cases occur before age 50?

Answer 36

A: Adenocarcinoma of the colon is the most common malignancy of the gastrointestinal tract.

A: The incidence of colorectal cancer peaks at 60 to 70 years of age, with fewer than 20% of cases occurring before age 50.

Question 37

Q: What are the risk factors for colorectal cancer (CRC)?

Q: What are the three patterns of presentation for colorectal cancer (CRC)?

Answer 37

A: The risk factors for CRC are both environmental and inherited. Environmental risk factors include a low intake of unabsorbable vegetable fiber and a high intake of refined carbohydrates and fat.

A: The three patterns of presentation for CRC are:

Sporadic
Inherited
Familial

Question 38

Q: What types of abnormalities are involved in the pathogenesis of colorectal carcinoma (CRC)?

Q: How many genetic pathways have been described in the development of CRC, and what are they?

Answer 38

A: The pathogenesis of colorectal carcinoma involves both genetic and epigenetic abnormalities.

A: At least two genetic pathways have been described in the development of CRC:

*The APC/β-catenin pathway, activated in the classic adenoma-carcinoma sequence.

*The microsatellite instability pathway, associated with defects in DNA mismatch repair and accumulation of mutations in microsatellite repeat regions of the genome.

Question 39

Q: What is the role of the APC/β-catenin pathway in CRC?

Q: What is the significance of the microsatellite instability pathway in CRC?
A

Answer 39

A: The APC/β-catenin pathway is involved in the classic adenoma-carcinoma sequence, accounting for up to 80% of sporadic colon tumors. It typically includes mutation of APC early in the neoplastic process.

: The microsatellite instability pathway is significant in CRC as it involves defects in DNA mismatch repair and leads to the accumulation of mutations in microsatellite repeat regions of the genome.

Question 40

Q: What common epigenetic event is involved in CRC, and what is its effect?

Answer 40

A: The most common epigenetic event involved in CRC is methylation-induced gene silencing, which contributes to the stepwise accumulation of multiple mutations.

Question 41

Q: How are adenocarcinomas distributed throughout the colon?

Q: How do tumors in the proximal colon typically grow, and what is a notable feature of these tumors?

Answer 41

A: Adenocarcinomas are distributed approximately equally over the entire length of the colon.

A: Tumors in the proximal colon often grow as polypoid or exophytic masses that extend along one wall of the large-caliber cecum and ascending colon. These tumors rarely cause obstruction

Question 42

Q: How do carcinomas in the distal colon typically present, and what complications can they cause?

Q: What are the two most important prognostic factors in colorectal adenocarcinoma?

Answer 42

A: Carcinomas in the distal colon tend to be annular lesions that produce “napkin-ring” constrictions and luminal narrowing, which can sometimes lead to obstruction.

A: The two most important prognostic factors in colorectal adenocarcinoma are the depth of invasion and the presence or absence of lymph node metastases.

Question 43

Q: What is the purpose of screening for colorectal cancer (CRC)?

Q: What are the two main types of CRC screening tests?

Answer 43

A: Screening for colorectal cancer aims to find the disease in people who have no symptoms, to find and remove polyps before they become cancerous, and to detect CRC early when it is small and likely has not spread, making treatment more effective.

A: The two main types of CRC screening tests are visual exams and stool-based tests.

Question 44

Q: What are some examples of visual exams used for CRC screening?

Answer 44

A: Examples of visual exams used for CRC screening include:

Flexible sigmoidoscopy
Colonoscopy
CT colonography (“virtual colonoscopy”)

Question 45

Q: What are some examples of stool-based tests used for CRC screening?

Answer 45

A: Examples of stool-based tests used for CRC screening include:

Fecal immunochemical test (FIT)
Guaiac-based fecal occult blood test (gFOBT)
Stool DNA tests (sDNA)

Question 46

Q: How is the anal canal anatomically divided, and what types of epithelia line each zone?

Answer 46

A: The anal canal is divided into thirds:

The upper zone is lined by columnar rectal epithelium.
The middle third is lined by transitional epithelium.
The lower third is lined by stratified squamous epithelium.

Question 47

Q: What types of differentiation can carcinomas of the anal canal exhibit?

Answer 47

A: Carcinomas of the anal canal can exhibit glandular, transitional, basaloid, or squamous patterns of differentiation.

Question 48

Q: What is the term used when an anal canal tumor displays a basaloid pattern throughout?

Q: What may basaloid differentiation in anal canal tumors be mixed with?

Answer 48

A: When an anal canal tumor displays a basaloid pattern throughout, it is referred to by the archaic term cloacogenic carcinoma.

A: Basaloid differentiation in anal canal tumors may be mixed with squamous or mucinous differentiation.

Question 49

Q: What is pure squamous cell carcinoma of the anal canal frequently associated with?

Q: What factor is crucial for determining the prognosis of anal canal tumors?

Answer 49

A: Pure squamous cell carcinoma of the anal canal is frequently associated with HPV infection, which also causes precursor lesions such as condyloma acuminatum.

A: The prognosis of anal canal tumors depends on the AJCC stage of the tumor.

Question 50

47 A 19-year-old man is advised by other
family members to see his physician because
genetic screening has detected a disease in
other family members.
 On physical examination, a stool sample is
positive for occult blood.
 A colonoscopy is performed, followed by a
colectomy.
 The figure shows the gross appearance of the
mucosal surface of the colectomy specimen.
Molecular analysis of this patient’s normal
fibroblasts is most likely to show a mutation in
which of the following genes?
 □ (A) APC
 □ (B) p53
 □ (C) K-RAS
 □ (D) HNPCC
 □ (E) NOD2

Answer 50

 47 (A) This young patient’s colon shows hundreds of polyps.
 This is most likely a case of familial adenomatous polyposis (FAP) syndrome, which results from inheritance of one mutant copy of the APC tumour-suppressor gene (a
few FAP cases are associated with DNA mismatch repair genes).

 Every somatic cell of this patient most likely has one defective copy of the APC gene.

 Polyps are formed when the second copy of the APC gene is lost in many colon epithelial cells.

 Without treatment, colon cancers arise in 100% of these patients because of accumulation of additional mutations in one or more polyps, typically before 30 years of age.

 Patients with the gene for hereditary nonpolyposis colorectal carcinoma also have an inherited susceptibility to develop colon cancer, but in contrast to patients with FAP,
they do not develop numerous polyps.

 Sporadic colon cancers may have CpG island Hypermethylation along with K-RAS mutations, while others have p53 mutations, but the somatic cells of patients with
these cancers do not show abnormalities of these genes.