ABSTRACT

Cancer is identified as the most dreadful disease of era. Inspite of the numerous researches on its
pathogenesis. Diagnostic and prognostic aspects it still remains an enigma. This necessitates
the availability of accurate diagnostic means to detect various malignancies in their
premalignant state. Study of tumor markers has given a new hope in this field but
application of these markers in understanding the pathogenesis, diagnosis and prognosis of
malignancies has not yet been fully established and requires a further improvement,
refinement and accuracy in the studies.
Definition
Tumor marker is defined as those biologic substances synthesized and released by tumor cells or
produced by the host in response to presence of cancerous tissue.
!

They are the biochemical indicators of the presence of a tumor. The term usually refers to a
molecule that can be detected in saliva, serum, in the cell membranes and the cytoplasm. A
variety of substances including enzymes, hormones, antigens and proteins may be called as
tumor markers.
1

They cannot be used as primary modalities for diagnosis of cancer but their main
utility is in confirming the diagnosis and for monitoring the prognosis during follow up
. 1


Characteristics of an ideal tumor marker

a. It should be produced by the tumor cells and be readily detected in body fluid
b. It should be present frequently enough and early enough in the development of
malignancy to be useful in screening for that cancer.
c. It should not be present in health or benign diseases.
d. The quantity of T should directly reflect the bulk of malignancy and be detectable
even when there is no evidence of tumor.
e. It should permit detection of early recurrence and metastasis.
f. The level of T should correlate with the results of anticancer therapy.

C"#SSI$IC#TI%&S
According to 'ancroft, (n)inger and *ichard, more specific markers are given which are according
to cell of origin of tumors!
"#
1$ EPITHELIAL MARKERS
a. %ytokeratins
b. &pithelial membrane antigen
c. %arcinoembryonic antigen
d. &namelin ' Amelogenin
e. ()*#+
,} CONNECTIVE TISSUE MARKER
-imentin

"} MUSCLE MARKERS
a. .esmin
b. uscle actin
c. yogenin
d. yodi
#$ ENDOTHELIAL MARKERS
a. /actor -III related antigen
b. %. "1
c. %. "#
d. 0odoplanin
e. -ascular endothelial growth factor

+} NEURAL MARKERS
a. 1122 protein
b. %. +3
c. 4euron specific &nolase
d. 4eurofilament protein
e. 5lial fibrillary acidic protein
f. 4erve growth factor receptor
6$ NEUROENDOCRINE MARKERS
a. 1ynaptophysin
b. %hromogranin
3} LYMPHOID MARKERS
a. T*%ell lymphoid marker
%."
%.#"
%. #+*78
b. )*%ell lymphoid marker
%. ,2
%. 39a
%. #+*7A
%. 12
c. (odgkin:s lymphoma
%. 1+
%. ,2
%. "2
%. #+*7A
d. Anaplastic large cell lymphoma
%. "2
Alk*1


;$ APOPTOTIC MARKERS
a. )cl*, family
b. 0 +" *
9} CELL ADHESION MOLECULES
a. %adherins
b. 1electins
c. Integrins
d. 1yndecans
e. %alcium independent adhesion molecules
12} BONE MARKERS
a. %. 99
b. 8steocalcin
c. Alkaline 0hosphatase
d. )one orphogenic protein
11} METASTATIC TUMOR MARKERS
a. %k 3 and %k ,2
b. -illin
+,,,-

"./01%ID /#*2(*S

13 T "ymphoid Cell /arker
a. CD3: The %." or T" antigen is a group of five different polypeptides of molecular
weight range 16*,; k .. The ma<ority of antibodies recognize the ,2 k . chain.
%." antibody binding to T cells induces calcium influ= and proliferation, leading
to the view that %." molecule group are involved in intracellular signaling
following antigen binding to the T cell receptor.
6
b. CD43:. The %.#" molecule, leucosialin, is a surface glycoprotein present on T
cells, monocytes, granulocytes and red cells. It is used as T cell marker but it is
present in some forms of low*grade ) cell lymphomas. It is used to confirm tumors
of T cell lineage.
6,3
c. CD45 RO: It denotes a 1;2 k . isoform of %.#+ found on ma<ority of T cells,
minor subsets of ) cell and monocytes. ost Tcell lymphomas can be identified
with antibody to %.#+ 78, fewer than 1> of ) cell lymphomas are reactive. Anti
%.#+ cocktail is particularly useful in the evaluation of undifferentiated round cell
tumors, because it stains lymphoma but not carcinoma, sarcoma or melanoma. It is
most widely used marker.
6,3
43 ' Cell "ymphoid /arkers5
a. CD20 ? The %.,2 denotes a "+ k . molecular weight molecule present on )
@ymphoid cells. It appears relatively late during ) cell mutation but persists to the
preplasma cell stage and is regarded as a highly specific ) cell marker., staining
appro=imately 9+> of these cells. Its gene is present on chromosome 11,q1,*q1".
the antibody @,6 is most widely used %.,2 antibody which recognizes the
ma<ority of malignant lymphomas of ) cell type and some lymphomas that are non
reactive to anti*%.#+. @,6 is believed to be reactive to an intracellular membrane
associated epitope of %.,2 antigen.
;
b. CD79a: This may be detected and used for confirmation of ) cell lineage in some
unusual ) cell lymphomas where there is no detectable e=pression of %.,2.%.39a
is a dimeric protein that is part of the ) cell receptor comple=. It is e=pressed early
in ) cell development and persists to the plasma cell stage.
;

c. CD45RA: The %.#+7A isoform is found on ) cells, monocytes and a subset of T
cells. It is a ,,2 k . isoform, which show reactivity to antibodies in formalin fi=ed
tissues. ost ) cell lymphomas can be recognized by using this marker.
9
d. CD10 ? It is a membrane*associated enzyme, neutral endopeptidase, which is
e=pressed on normal pre ) cells, follicle center cells and a subpopulation of
thymocytes. %.12 is used in some research centers on frozen tissue to assist in the
classification of ) cell lymphomas.
3,;
+3 1odgkin6s Cell /arkers
a. CD15: It is a carbohydrate antigen previously referred to as hapten A, composed of
galactose, fucose and 4*acetyl* glucosamine linked in a specific sequence. It is
present in the secondary granules of myeloid cells and e=pression seen in myeloid
and some monocytic malignancies, (odgkin:s cells and some high grade T and )
cell lymphomas. %.1+ is e=pressed by the 7eed 1ternberg cells and is used in the
identification of (odgkin:s disease.
3,;
b. CD30: The %."2 antigen is a transmembrane glycoprotein of molecular weight 92
k .. it can be modified by the addition of 1+ k . or " k . molecules. The
antibodies ki1 and )er (, recognizes different epitopes present on the precursor
and mature molecules. %."2 appears to be a marker of lymphoid cell activation
and is found in (odgkin:s and anaplastic large cell lymphoma cells. )er(, is the
most widely used antibody to %."2.
9


,3 #naplastic "arge Cell "ymphomas
a. CD+7 ? embrane e=pression of %."2 by tumor cells of anaplastic large cell
lymphomas is considered to be an important diagnostic tool.
9
b. #lk 8! Anaplastic large cell lymphomas also e=press cytoplasmic aberrant
tyrosine kinase related to chromosomal translocations, usually t B,?+C. Antibody
Alk*1 to this enzyme is found to be useful in the identification of ma<ority of these
lesions.
9
-3 /iscellaneous
The diagnosis of ) cell differentiated lymphomas, especially plasmacytoid forms, can
be confirmed through the identification of a monoclonal kappa or gamma population. 1ignificant
alteration in the normal "2>? 32> kappa? gamma ratio typical of non*neoplastic ) cell
populations would be strong evidence of a monoclonal population of cells.
12
Terminal deo=ynucleotidyl transferase BTdtC is an enzyme that may be e=pressed by
acute leukemia cells especially those of acute myeloid and lymphoblastic leukemias.
Immunohistochemical staining can be helpful in the identification of leukemic infiltrates in oral
tissues, and it may aid in separation of leukemias from lymphomas. )ut, caution should be taken,
because not all acute leukemias will e=press it.
9,12
5ranulocytic differentiation can be confirmed with antibody to myelopero=idase, %.6; is
an intracytoplasmic lysosomal molecule present in myeloid, histiocytes and mast cells. It is
highly e=pressed by macrophages and neutrophils. D01 seems to be the most reliable antibody
for detection of antigen. 8ther macrophage associated antibodies E ie, A% ";3, (A*+3,05*
1 $ are less commonly used but are available for confirmation if necessary. %.66 is found in
granulocytes and myeloid precursors and may be consequently recognize a wide range of cell
types including glandular epithelial cells and their tumors. %.61 has specific reactivity with
thrombocytes, megakaryocytes and megakaryoblast.
12
C%&C"9SI%&S
.%ancer is a genetics disease. .yregulation between the growth promoting and inhibitory
signals lies at the heart of carrion genesis. 8ver e=pression of 8ncogenes such as p+" and
altered e=pression of apoptotic protein may serve as an important tumor markers, which have
the potential course and outcome.
Thus, the tumor marker has potential to find application beyond the field of diagnoses, which
can be e=plained as?
1. An aid in deciding the treatment modality of the patient.
,. In detection of metastasis or occult malignancy.
". To study the response of the patient to the therapy and to detect the recurrence at an
earlier stage.
#. To predict the prognosis.
It is likely that, in the future these methods will increasingly enter into the day*to*day
diagnosis and management of patients. the pathologist will continue to play a fundamental role in
diagnosis and will likely be in a pivoted position to guide the implementation and interpretation
of these tests as they move from the research laboratory into diagnostic pathology .
7ecent advances in defining these fundamental mechanisms of tumor biology through
tumor markers may allow prevention, diagnosis and treatment of cancer to be approached at the
molecular level. (owever, because the nomenclature of molecular oncology has become
increasingly distant from the language of the clinician .we as the pathologists should be able to
translate and evaluate the goals and success of these new diagnostics and therapeutic strategies.
9,12
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