Tumors/Polyps of IntestineNon-neoplastic polyps of intestine

AdenomasColorectal carcinoma

Lecture 16

Polyp• A polyp is a mass that

protrudes into the lumen of the gut.

• Stalked or pedunculated polyp• Sessile polyp

Tumors of the Small and Large Intestines

Non-neoplastic Polyps 90%Hyperplastic polyps- most commonHamartomatous polypsJuvenile polypsPeutz-Jeghers polypsInflammatory polypsLymphoid polyps

• Neoplastic Epithelial Lesions• Benign polyps• Adenomas• Malignant lesions

Adenocarcinoma Squamous cell carcinoma of the anus

• Other tumors• Gastrointestinal stromal tumors• Carcinoid tumors• Lymphoma

Non-neoplastic polyps of intestine

• The overwhelming majority of intestinal polyps occur sporadically, particularly in the colon, and increase in infrequency with age.

• Non-neoplastic polyps represent 90% of all epithelial polyps in the large intestine and are found in more than half of all persons age 60 years or older.

Hyperplastic PolypsColonic hyperplastic polyps are common

epithelial proliferations that are typically discovered in the sixth and seventh decades of life.

Pathogenesis The pathogenesis of hyperplastic polyps is

incompletely understood, but they are thought to result from decreased epithelial cell turnover and delayed shedding of surface epithelial cells, leading to a “piling up” of goblet cells and absorptive cells.

• It is now appreciated that these lesions are without malignant potential. Their chief significance is that they must be distinguished from sessile serrated adenomas, histologically similar lesions that have malignant potential.

• It is also important to remember that epithelial hyperplasia can occur as a nonspecific reaction adjacent to or overlying any mass or inflammatory lesion and, therefore, can be a clue to the presence of an adjacent, clinically important lesion.

Hyperplastic Polyps cont.• Most common non-neoplastic polyp in the colon• Do not exhibit dysplasia• Proliferation is mainly in the basal portion of the crypt(used to distinguish from adenomas)• Typically located in the rectosigmoid and are < 5mm

insize• Small left sided HP are not a significant marker ofcolon cancer risk and finding them on sigmoidoscopy isNOT a routine indication for colonoscopy

• When single, they do not have malignant potential. Sessile serrated adenoma may have malignant potential. They are small, nipple-like, hemispherical, smooth protrusions of the mucosa. They may occur singly but are more often multiple. Although they may be anywhere in the colon, well over half are found in the rectosigmoid region.

MorphologyHyperplastic polyps are most commonly found in the

left colon and are typically less than 5 mm in diameter. They are smooth, nodular protrusions of the mucosa, often on the crests of mucosal folds. They may occur singly but are more frequently multiple, particularly in the sigmoid colon and rectum.

• Histologically, hyperplastic polyps are composed of mature goblet and absorptive cells. The delayed shedding of these cells leads to crowding that creates the

serrated surface architecture that is the morphologic hallmark of these lesions.

• they contain • abundant crypts • lined by well-differentiated goblet or

absorptive epithelial cells, • separated by a scant lamina propria.

Hyperplastic polyp. A, Polyp surface with irregular tufting of epithelial cells. B, Tufting results from epithelial overcrowding. C, Epithelial crowding produces a serrated architecture

when glands are cut in cross-section.

Hamartomatous polyps• Hamartomatous polyps occur sporadically and in

the context of various genetically determined or acquired syndromes . Recall that hamartomas are tumor-like growths composed of mature tissues that are normally present at the site in which they develop. Although Hamartomatous polyposis syndromes are rare, they are important to recognize because of associated intestinal and extra-intestinal manifestations and the possibility that other family members are affected.

Juvenile Polyps• Juvenile polyps are focal malformations of

the mucosal epithelium and lamina propria. These may be sporadic or syndromic, but the morphology of the two forms may be indistinguishable. The vast majority of juvenile polyps occur in children less than 5 years of age. When present in adults, polyps with identical morphology are sometimes confusingly referred to as inflammatory polyps.

• The majority of juvenile polyps are located in

the rectum and most present with rectal bleeding. In some cases prolapse occurs and the polyp protrudes through the anal sphincter. Sporadic juvenile polyps are usually solitary lesions and may be referred to as retention polyps.

• In contrast, individuals with the autosomal dominant syndrome of juvenile polyposis have from 3 to as many as 100 hamartomatous polyps and may require colectomy to limit the chronic and sometimes severe hemorrhage associated with polyp ulceration. A minority of patients also have polyps in the stomach and small bowel. Pulmonary arteriovenous malformations are a recognized extra-intestinal manifestation of the syndrome.

Morphology Most juvenile polyps are less than 3 cm in diameter.

They are typically pedunculated, smooth-surfaced, reddish lesions with characteristic cystic spaces apparent after sectioning.

Microscopic examination shows these cysts to be dilated glands filled with mucin and inflammatory debris . The remainder of the polyp is composed of lamina propria expanded by mixed inflammatory infiltrates. The muscularis mucosa may be normal or attenuated.

Juvenile polyposis. A, Juvenile polyp. Note the surface erosion and cystically dilated crypts. B, Inspissated mucous, neutrophils, and inflammatory debris can

accumulate within dilated crypts.

• Although the morphogenesis of juvenile polyps is incompletely understood, some have suggested that mucosal hyperplasia is the initiating event. This hypothesis is consistent with the discovery that mutations in pathways that regulate cellular growth cause autosomal dominant juvenile polyposis. The most common mutation identified is of SMAD4, which encodes a cytoplasmic intermediate in the TGF-β signaling pathway. BMPR1A, a kinase that is a member of the TGF-β superfamily, may be mutated in other cases.

However, these mutations account for fewer than half of patients, suggesting that changes in other genes can also cause juvenile polyposis. Dysplasia occurs in a small proportion of juvenile polyps, and the juvenile polyposis syndrome is associated with an increased risk of colonic adenocarcinoma.

Hamartomatous Juvenile polyps• Hamartomatous proliferations, mainly of the

lamina propria, enclosing widely spaced, dilated cystic glands. They occur most frequently in children younger than 5 years old but are also found in adults of any age; in the latter group they may be called retention polyps.

large in children (1-3 cm in diameter) but smaller in adults;

they are rounded , smooth, or slightly lobulated and sometimes have a stalk as long as 2 cm.

• In general, they occur singly and in the rectum, and being Hamartomatous they have no malignant potential.

• Juvenile polyps may be the source of rectal bleeding and in some cases become twisted on their stalks to undergo painful infarction.

Peutz-Jeghers Syndrome • This rare autosomal dominant syndrome

presents at a median age of 11 years with multiple GI hamartomatous polyps and mucocutaneous hyperpigmentation. The latter takes the form of dark blue to brown macules around the mouth, eyes, nostrils, buccal mucosa, palmar surfaces of the hands, genitalia, and perianal region. These lesions are similar to freckles but are distinguished by their presence in the buccal mucosa.

• Peutz-Jeghers polyps can initiate intussusception, which is occasionally fatal. Of greater importance, Peutz-Jeghers syndrome is associated with an increased risk of several malignancies, including cancers of the colon, pancreas, breast, lung, ovaries, uterus, and testicles, as well as other unusual neoplasms, such as sex cord tumors.

Pathogenesis

Germline heterozygous loss-of-function mutations in the gene LKB1/STK11 are present in approximately half of individuals with familial Peutz-Jeghers syndrome as well as a subset of patients with sporadic PeutzJeghers syndrome. LKB1/STK11 is a kinase that regulates cell polarization, growth, and metabolism.

The function of the second “normal” copy of LKB1/STK11 is often lost through somatic mutation in cancers occurring in Peutz-Jeghers syndrome, consistent with the view that LKB1/STK11 is a tumor suppressor gene and providing an explanation for the high risk of neoplasia in affected patients. The GI adenocarcinomas arise independently of the hamartomatous polyps, indicating that the hamartomas are not preneoplastic precursor lesions.

MorphologyThe polyps of Peutz-Jeghers syndrome are most

common in the small intestine, although they may occur in the stomach and colon, and, with much lower frequecy, in the bladder and lungs. Grossly, the polyps are large and pedunculated with a lobulated contour. Histologic examination demonstrates a characteristic arborizing network of connective tissue, smooth muscle, lamina propria, and glands lined by normal-appearing intestinal epithelium .

The arborization and presence of smooth muscle intermixed with lamina propria are helpful in distinguishing polyps of Peutz-Jeghers syndrome from juvenile polyps.

Peutz-Jeghers polyp. A, Polyp surface (top) overlies stroma composed of smooth muscle bundles cutting through the lamina propria. B, Complex glandular architecture and the presence of smooth muscle are features that distinguish Peutz-Jeghers polyps from juveni le

polyps.

Clinical Features Because the morphology of Peutz-Jeghers

polyps can overlap with that of sporadic hamartomatous polyps, the presence of multiple polyps in the small intestine, mucocutaneous hyperpigmentation, and a positive family history are key to the diagnosis. Detection of LKB1/STK11 mutations can be helpful diagnostically in patients with polyps who lack mucocutaneous hyperpigmentation.

However, the absence of LKB1/STK11 mutations does not exclude the diagnosis, since mutations in other presently unknown genes can also cause the syndrome. Because of the increased risk of cancer, routine surveillance of the GI tract, pelvis, and gonads is typically recommended.

Cowden syndrome and Bannayan-Ruvalcaba-Riley syndrome

are autosomal dominant hamartomatous polyp syndromes associated with loss-of-function mutations in PTEN, a gene encoding a lipid phosphatase that inhibits signaling through the PI3K/AKT pathway. PTEN, a well-characterized tumor suppressor, is also mutated in a small number of patients presenting with juvenile polyposis.

• The multiple syndromes associated with PTEN mutations are sometimes grouped together under the heading “PTEN hamartoma syndrome.” The basis for the differing presentations of these syndromes is not understood; interaction of PTEN loss-of-function mutations with other unknown modifying genes is suspected.

• Cowden syndrome is characterized by macrocephaly, intestinal hamartomatous polyps, and benign skin tumors, typically trichilemmomas, papillomatous papules, and acral keratoses. A variety of other lesions derived from all three embryologic layers, including subcutaneous lipomas, leiomyomas, and hemangiomas, also occur. While individuals with Cowden syndrome do not have increased risk of GI malignancy, they are predisposed to breast carcinoma, follicular carcinoma of the thyroid, and endometrial carcinoma.

• Bannayan-Ruvalcaba-Riley syndrome can be distinguished from Cowden syndrome on clinical grounds; for example, mental deficiencies and developmental delays are only seen with the Bannayan-Ruvalcaba-Riley syndrome, which also seems to be associated with a lower incidence of neoplasia than Cowden syndrome. Features shared by these two syndromes include GI hamartomatous polyps, lipomas, macrocephaly, hemangiomas, and, in males, pigmented macules on the glans penis.

Cronkhite-Canada Syndrome • Cronkhite-Canada syndrome contrasts sharply

with other hamartomatous polyposis syndromes in that it is nonhereditary and most often develops in individuals over 50 years of age. The clinical symptoms are nonspecific and include diarrhea, weight loss, abdominal pain, and weakness. The most characteristic feature is the presence of hamartomatous polyps of the stomach, small intestine, and colorectum that are histologically indistinguishable from juvenile polyps.

• However, the nonpolypoid intervening mucosa also shows cystic crypt dilatation and lamina propria edema and inflammation. Associated abnormalities include nail atrophy and splitting, hair loss, and areas of cutaneous hyperpigmentation and hypopigmentation. The cause of Cronkhite-Canada syndrome is unknown, and no specific therapies are available. Supportive nutritional therapy, which alleviates cachexia and anemia, can occasionally induce remission. Nonetheless, as many as 50% of cases are fatal.

Inflammatory Pseudopolyps

• A projecting mass of hypertrophied mucous membrane

• Irregularly shaped islands of residual intactcolonic mucosa that are the result of themucosal ulceration and regeneration that occursin IBD (benign with no malignant potential).• Usually multiple, filiform and scatteredthroughout the colitic region of the colon

(Ulcerative Colitis)

A projecting mass of hypertrophied mucous membrane (as in the stomach or colon) resulting from local inflammation

• The polyp that forms as part of the solitary rectal ulcer syndrome is an example of a purely inflammatory lesion. Patients present with a clinical triad of rectal bleeding, mucus discharge, and an inflammatory lesion of the anterior rectal wall.

• The underlying cause is impaired relaxation of the anorectal sphincter that creates a sharp angle at the anterior rectal shelf and leads to recurrent abrasion and ulceration of the overlying rectal mucosa. An inflammatory polyp may ultimately form as a result of chronic cycles of injury and healing. Entrapment of this polyp in the fecal stream leads to mucosal prolapse.

• Thus, the distinctive histologic features are those of a typical inflammatory polyp with superimposed mucosal prolapse and include lamina propria fibromuscular hyperplasia, mixed inflammatory infiltrates, erosion, and epithelial hyperplasia

Solitary rectal ulcer syndrome. A, The dilated glands, proliferative epithelium, superficial erosions, and inflammatory infiltrate are typical of an inflamatory polyp. However, the smooth muscle hyperplasia within the lamina propria suggests that mucosal prolapse has also occurred. B, Epithelial hyperplasia. C, Granulation

tissue-like capillary proliferation within the lamina propria caused by repeated erosion and re-epithelialization.

Submucosal Polyps• Lymphoid aggregates, lipomas, leiomyomas,pneumatosis cystoid intestinalis, hemangiomas,fibromas, carcinoids, and metastatic lesions• Can be neoplastic or non-neoplastic• Smooth overlying mucosa• Lipoma can be diagnosed endoscopically because

of its yellow color and softness (pillow sign)• EUS can be useful in defining the site of origin and

for biopsy of submucosal lesions if the diagnosis is in doubt.

Neoplastic

Polyps

Adenomas

Adenomatous Polyps

2/3 of colonic polyps are adenomas By definition they are dysplastic and have

malignant potential Time for development of adenomas to cancer is

about 7 to 10 years.

Adenomas

Advanced adenoma

high grade dysplasia or adenoma that is > 10 mm in size or with villous component.

Synchronous adenoma

adenoma that is diagnosed at same time as index colorectal neoplasm

Metachronous adenoma

diagnosed at least six months after diagnosis of previous adenoma.

Epidemiology of Adenoma Older age is a major risk factor More common in men Large adenomas (> 9mm) may be more

common in African Americans African Americans have a higher risk of right-

sided colonic adenomas and may present with cancer at a younger age (< 50 years) than

Caucasians.

• The prevalence of colonic adenoma is 20% to 30% before age 40, rising to 40 to 60 % after age 60. Males and females are affected equally???.

• There is a well-defined familial predisposition to sporadic adenomas, accounting for about a fourfold greater risk for adenomas among first degree relatives, and also a fourfold greater risk of colorectal carcinoma in any person with adenomas.

• All adenomatous lesions arise as the result of epithelial proliferation and dysplasia, which may range from mild to severe as to represent transformation to carcinoma. Furthermore, there is strong evidence that most sporadic invasive colorectal adenocarcinomas arise in preexisting adenomatous lesions.

Types of adenomas on the basis of the epithelial architecture

• 1. Tubular adenomas• 2. Villous adenomas• 3. Tubulovillous adenomas • 4. Sessile Serrated adenomas

Endoscopic Classification 1. Sessile – base is attached to colon wall usually

large2. Pedunculated – mucosal stalk is interposed

between the polyp and the wall 3. Flat – height less than one-half the diameter ofthe lesion. Depressed lesions appear to be particularly likelyto harbor high-grade dysplasia or be malignanteven if small.

Pathologic Classification I. Low grade dysplasia: characterized by branching crypts lined by cells with long, thin nuclei that begin to

stratify, resulting in increased nucleus-to-cytoplasm ratio and a loss of normal goblet cells.

II. High grade dysplasia: do not contain invasive malignancy, which is defined by breach of the muscularis mucosa by neoplastic cells.

Represents an intermediate step in the evolution from low grade adenomatous polyp to cancer

Not associated with metastasis since there are no lymphatic vessels in the lamina propria..

Tubular Adenoma

The most common, account for more than 80 percent of colonic adenomas.

Characterized by a complex network of branching adenomatous glands.

Most TA are small and pedunculated.

Morphology of TA

May arise anywhere in the colon, but about half are found in the rectosigmoid, the proportion increasing with age.

In about half of the instances they occur singly, but in the remainder two or more lesions are distributed at random.

• The smallest adenomas are sessile; lesions 0.3 cm in size can be identified at endoscopy. Among the larger tubular adenomas up to 2.5 cm in diameter, most have slender stalks 1 to 2 cm long and raspberry –like heads.

• Histologically the stalk is covered by normal colonic mucosa, but the head is composed of neoplastic epithelium, forming branching glands lined by tall, hyperchromatic, somewhat disorderly cell, which may or may not show mucin secretion.

• In some instances there are small foci of villous architecture.

• In the clearly benign lesion, the branching glands are well separated by lamina propria, and the level of dysplasia or cytologic atypia is slight.

• However all degrees of dysplasia may be encountered, ranging up to cancer confined to the mucosa (intramucosal carcinoma) or invasive carcinoma extending into the mucosa of the stalk.

• A frequent finding in any adenoma is superficial erosion of the epithelium, the result of mechanical trauma.

Villous adenomasVillous: account for 5 to 15 percent of

adenomas. They are characterized by glands that are long and extend straight down from the surface to the center of the polyp, creating finger-like projections. Villous adenomas tend to be large and sessile.

• Morphology of VA: Villous adenomas are the larger and more ominous of the epithelial polyps. They tend to occur in older persons, most commonly in the rectum and rectosigmoid, but they may be located elsewhere. They generally are sessile, up to 10 cm in diameter, velvety or cauliflower-like masses projecting 1 to 3 cm above the surrounding mucosa.

• The histology is that of frondlike villiform extensions of the mucosa covered by dysplastic, sometimes very disorderly, sometimes piled-up, columnar epithelium. All degrees of dysplasia may be encountered, and invasive carcinoma is found in as many as 40% of these lesions, the frequency being correlated with the size of the polyp.

Tubulovillous adenomas

TVA: having 26 to 75 percent villous componentaccount for 5 to 15 percent of adenomas;

combination of above. Tubulovillous adenomas are composed of a broad mix of tubular and villous areas. They are intermediate between the tubular and the villous lesions in their frequency of having a stalk or being sessile, their size, the degree of dysplasia, and the risk of harboring intramucosal or invasive carcinoma.

Serrated Polyps Display features of both hyperplastic and

adenoma Were classified in past as HP and benign but new evidence shows that they may behave as adenomas

No guidelines for management; it is generally recommended that surveillance intervals should follow that of other adenomas

Two types Sessile serrated adenoma – precursors to large

HP in proximal colon of patients with hyperplastic polyposis

Traditional serrated adenoma – look and behave as conventional adenomas; often pedunculated found more often in distal colon

Clinical features of adenomas• The smaller adenomas are usually

asymptomatic, until such time that occult bleeding leads to clinically significant anemia.

• Villous adenomas are much more frequently symptomatic because of overt or occult rectal bleeding. The most distal villous adenomas may secrete sufficient amounts of mucosal material rich in protein and potassium to produce hypoproteinemia or hypokalemia.

• On discovery, all adenomas, regardless of their location in the alimentary tract, are to be considered potentially malignant; thus, in practical terms, prompt and adequate excision is mandated.

• Familial Polyposis Syndromes

• Familial polyposis syndromes are uncommon• Autosomal dominant disorders. Their

importance lies in the propensity for malignant transformation and in the insights that such transformation has provided in unraveling the molecular basis of colorectal cancer.

• Individuals with familial adenomatous polyposis (FAP) typically develop 500 to 2500 colonic adenomas that carpet the mucosal surface; a minimum number of 100 is required for the diagnosis.

• Multiple adenomas may also be present elsewhere in the alimentary tract, including almost a 100 % lifetime incidence of duodenal adenomas.

• Most polyps are tubular adenomas; occasional polyps have villous features.

• Polyps usually become evident in adolescence or early adulthood. The risk of colonic cancer is virtually 100% by midlife, unless a prophylactic colectomy is performed.

Risk Factors for High grade dysplasia and cancer Adenomatous polyps > 1 cm in diameter are risk

factor for containing CRC Villous histology – adenomatous polyps with > 25percent villous histology are a risk factor for

developing CRC High-grade dysplasia – adenomas with high-grade

dysplasia often coexist with areas of invasive cancer in the polyp.

Number of polyps: three or more is a risk factor for development of metachronous adenomas with

advanced pathologic features.

Colorectal Carcinoma

Adenocarcinoma 98%

Intestinal tumorsNon-neoplastic Polyps

Hyperplastic polyps

Hamartomatous polyps

Juvenile polyps

Peutz-Jeghers polyps

Inflammatory polyps

Lymphoid polyps

Neoplastic Epithelial Lesions

Benign polyps

Adenomas

Malignant lesions

AdenocarcinomaSquamous cell carcinoma of the anus

Other Tumors

Gastrointestinal stromal tumors

Carcinoid tumor

Lymphoma

Epithelial tumors of the intestines:major cause of morbidity and mortality worldwide

Colon, including rectum:host to more primary neoplasms than any other organ in the body

AdenocarcinomaAdenocarcinoma is a cancer of an epithelium that originates in glandular tissue, adeno means gland.

• 98% of all cancers in large intestine almost always

arise in adenomatous polyps, generally curable by resection

Epidemiology

• peak incidence: 60 to 70 years of age• < 20% cases before age of 50

• adenomas – presumed precursor lesions for most tumors

• males affected ≈ 20% more often than females

Epidemiology

• worldwide distribution• highest incidence rates in United States,

Canada, Australia, New Zealand, Denmark, Sweden, and other developed countries

Etiology

• genetic influences:– preexisting ulcerative colitis or polyposis

syndrome– hereditary nonpolyposis colorectal cancer

syndrome (HNPCC, Lynch syndrome) → germ-line mutations of DNA mismatch repair genes

Etiology

• environmental influences:– dietary practices• low content of unabsorbable vegetable fiber• corresponding high content of refined carbohydrates• high fat content• decreased intake of protective micronutrients (vitamins

A, C, and E)

– use of Aspirin® and other NSAIDs: protective effect against colon cancer?• cyclooxygenase-2 & prostaglandin E2

Morphology

• 25% of colorectal carcinomas: in cecum or ascending colon

• similar proportion: in rectum and distal sigmoid

• 25%: in descending colon and proximal sigmoid

• remainder scattered elsewhere• multiple carcinomas present → often at

widely disparate sites in the colon

Morphology

• all colorectal carcinomas begin as in situ lesions• tumors in the proximal colon: polypoid, exophytic

masses that extend along one wall of the cecum and ascending colon

Morphology

• in the distal colon: annular, encircling lesions that produce “napkin-ring” constrictions of the bowel and narrowing of the lumen

• both forms of neoplasm eventually penetrate the bowel wall and may appear as firm masses on the serosal surface

Morphology

• all colon carcinomas - microscopically similar• almost all - adenocarcinomas• range from well-differentiated to undifferentiated,

frankly anaplastic masses• many tumors produce mucin• secretions dissect through the gut wall, facilitate

extension of the cancer and worsen the prognosis• cancers of the anal zone are predominantly squamous

cell in origin

Clinical Features • may remain asymptomatic for years• symptoms develop insidiously• cecal and right colonic cancers:

– fatigue– weakness– iron deficiency anemia

• left-sided lesions:– occult bleeding– changes in bowel habit– crampy left lower quadrant discomfort

• anemia in females may arise from gynecologic causes, but it is a clinical maxim that iron deficiency anemia in an older man means gastrointestinal cancer until proved otherwise

Clinical Features

• spread by direct extension into adjacent structures and by metastasis through lymphatics and blood vessels

• favored sites for metastasis:– regional lymph nodes– liver– lungs– bones– other sites including serosal

membrane of the peritoneal cavity

• carcinomas of the anal region → locally invasive, metastasize to regional lymph nodes and distant sites

TNM Staging of Colon Cancer

Tumor (T)T0 = none evidentTis = in situ (limited to mucosa)T1 = invasion of lamina propria or submucosaT2 = invasion of muscularis propriaT3 = invasion through muscularis propria into

subserosa or nonperitonealized perimuscular tissue

T4 = invasion of other organs or structures

Lymph Nodes (N)0 = none evident1 = 1 to 3 positive pericolic nodes2 = 4 or more positive pericolic nodes3 = any positive node along a named blood vessel

Distant Metastases (M)0 = none evident1 = any distant metastasis

5-Year Survival RatesT1 = 97%T2 = 90%T3 = 78%T4 = 63%Any T; N1; M0 = 66%Any T; N2; M0 = 37%Any T; N3; M0 = data not availableAny M1 = 4%

Clinical Features

• detection and diagnosis:– digital rectal examination– fecal testing for occult blood loss– barium enema, sigmoidoscopy and

colonoscopy– confirmatory biopsy– computed tomography and other

radiographic studies– serum markers (elevated blood

levels of carcinoembryonic antigen)

– molecular detection of APC mutations in epithelial cells, isolated from stools

– tests under development: detection of abnormal patterns of methylation in DNA isolated from stool cells

Therapy

• chemotherapy• radiotherapy• photodynamic therapy• radical surgery• gene therapy