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U N I T 1
Cell and Tissue Function
The serum markers that have proven most useful in
clinical practice are the human chorionic gonadotro-
pin (hCG), prostate-specific antigen (PSA), CA-125,
α
-fetoprotein (AFP), CD blood cell antigens, and car-
cinoembryonic antigen (CEA). The hCG is a hormone
normally produced by the placenta. It is used as a marker
for diagnosing, prescribing treatment, and following
the disease course in persons with high-risk gestational
trophoblastic tumors. Prostate-specific antigen (PSA)
is used as a marker in prostate cancer, and CA-125 is
used as a marker in ovarian cancer. Markers for leuke-
mia and lymphomas are grouped by so-called
clusters
of differentiation
(CD) antigens (see Chapter 15). The
CD antigens help to distinguish among T and B lympho-
cytes, monocytes, granulocytes, and natural killer cells
and immature variants of these cells.
2,3
Some cancers express fetal antigens that are nor-
mally present only during embryonal development and
induced to reappear as a result of neoplasia.
2
The two
that have proved most useful as tumor markers are alpha
fetoprotein (AFP) and CEA.
α
-fetoprotein is synthesized
by the fetal liver, yolk sac, and gastrointestinal tract and
is the major serum protein in the fetus. Elevated levels
are encountered in people with primary liver cancers
and have also been observed in some testicular, ovarian,
pancreatic, and stomach cancers. Carcinoembryonic
antigen normally is produced by embryonic tissue in the
gut, pancreas, and liver and is elaborated by a number
of different cancers, including colorectal carcinomas,
pancreatic cancers, and gastric and breast tumors. As
with most other tumor markers, elevated levels of AFP
and CEA are found in other, noncancerous conditions,
and elevated levels of both depend on tumor size so that
neither is useful as an early test for cancer.
As diagnostic tools, tumor markers have limitations.
Nearly all markers can be elevated in benign conditions,
andmost are not elevated in the early stages of malignancy.
Furthermore, they are not in themselves specific enough
to permit a diagnosis of a malignancy, but once a malig-
nancy has been diagnosed and shown to be associated
with elevated levels of a tumor marker, the marker can be
used to assess progress of the disease. Extremely elevated
levels of a tumor marker can indicate a poor prognosis or
the need for more aggressive treatment. Perhaps the great-
est value of tumor markers is in monitoring therapy in
people with widespread cancer. The level of most cancer
markers tends to decrease with successful treatment and
increase with recurrence or spread of the tumor.
Cytologic, Histologic, and Gene-Profiling
Methods
Cytologic and histologic studies are laboratory meth-
ods used to examine tissues and cells. Several sampling
approaches are available including cytologic smears, tis-
sue biopsies, and needle aspiration.
2
Papanicolaou Smear.
The Pap smear is a cytologic
method that consists of a microscopic examination of a
properly prepared slide by a cytotechnologist or patho
logist for the purpose of detecting the presence of abnor-
mal cells. The usefulness of the Pap smear relies on the
fact that cancer cells lack the cohesive properties and
intercellular junctions that are characteristic of normal
tissue; without these characteristics, cancer cells tend to
exfoliate and become mixed with secretions surround-
ing the tumor growth. Although the Pap smear is widely
used as a screening test for cervical cancer, it can be per-
formed on other body secretions, including nipple drain-
age, pleural or peritoneal fluid, and gastric washings.
Tissue Biopsy.
Tissue biopsy involves the removal of
a tissue specimen for microscopic study. It is of criti-
cal importance in designing the treatment plan should
cancer cells be found. Biopsies are obtained in a number
of ways, including needle biopsy; endoscopic methods,
such as bronchoscopy or cystoscopy, which involve the
passage of an endoscope through an orifice and into the
involved structure; and laparoscopic methods.
Fine needle aspiration involves withdrawing cells and
attendant fluid with a small-bore needle. The method
is most widely used for assessment of readily palpable
lesions in sites such as the thyroid, breast, and lymph
nodes. Modern imaging techniques have also enabled
the method to be extended to deeper structures such as
the pelvic lymph nodes and pancreas.
In some instances, a surgical incision is made from
which biopsy specimens are obtained. Excisional biop-
sies are those in which the entire tumor is removed. The
tumors usually are small, solid, palpable masses. If the
tumor is too large to be completely removed, a wedge
of tissue from the mass can be excised for examination.
A quick frozen section may be done and examined by a
pathologist to determine the nature of a mass lesion or
evaluate the margins of an excised tumor to ascertain
that the entire neoplasm has been removed.
3
Immunohistochemistry.
Immunohistochemistry inv
olves the use of monoclonal antibodies to facilitate
the identification of cell products or surface markers.
3
For example, certain anaplastic carcinomas, malignant
lymphomas, melanomas, and sarcomas look very simi-
lar under the microscope, but must be accurately iden-
tified because their treatment and prognosis are quite
different.
Immunohistochemistry can also be used to determine
the site of origin of metastatic tumors. Many cancer
patients present with metastasis. In cases in which the ori-
gin of the metastasis is obscure, immunochemical detec-
tion of tissue-specific or organ-specific antigens can often
help to identify the tumor source. Immunochemistry can
also be used to detect molecules that have prognostic or
therapeutic significance. For example, detection of estro-
gen receptors on breast cancer cells is of prognostic and
therapeutic significance because these tumors respond to
antiestrogen therapy.
Microarray Technology.
Microarray technology has
the advantage of analyzing a large number of molecu-
lar changes in cancer cells to determine overall patterns
of behavior that would not be available by conventional
means. The technique uses “gene chips” that can perform
