This document discusses tumor staging and biomarkers for oral cancer. It introduces the TNM staging system and its components for assessing tumor size, lymph node involvement, and metastasis. It also addresses limitations of staging and types of biomarkers that can be used, including commonly used ones like CD44, interleukin levels, and tissue polypeptide antigen. Biomarkers can help with screening, diagnosis, prognosis, and monitoring treatment response for oral cancer.
2. Introduction
Aims of staging
Method of staging
Stage grouping
Limitations of staging
Types of Biomarkers
Commonly used biomarkers
Conclusion
References
3. (a) cancer cells are derived from the body’s own cells
(b) cancer cells generally continue to grow in an
unlimited fashion, at least when they have reached a
size that leads to their being diagnosed
(c) they often infiltrate, i.e. they grow into and destroy
the surrounding normal tissue
(d) they can spread via blood and/or lymphatic vessels
and cause secondary growths- known as metastases-
in other organs.
In general, malignant neoplasms in humans and
rodents develop through multistep processes During
such processes, several genetic alterations occur
4. The tumor-node-metastasis (TNM) staging system was first
reported by Pierre Denoix in the 1940.
The International Union Against Cancer (UICC) eventually
adapted the system and compiled the first edition of the TNM
staging system in 1968 for 23 body sites.
TNM staging system is simply an anatomic staging system
that describes the anatomic extent of the primary tumor as
well as the involvement of regional lymph nodes and distant
metastasis
The overwhelming majority of mucosal HNCs are squamous
cell carcinomas. Therefore, the TNM classification of the UICC
and the American Joint Committee on Cancer (AJCC) for most
mucosal anatomic sites is designed for squamous cell
carcinoma and minor salivary gland cancers.
5. Why staging?
An aid to planning therapy
Indication of prognosis
Comparison of results of treatment
Facilitate exchange of information between
treatment centres
Statistics and trends
6. T –Extent of primary tumour
N –Presence or absence and extent of
nodal involvement
M –Presence or absence of distant
metastasis
23. Limitation of T Staging
crude system
Tumour size not consistently related to
prognosis
Debatable anatomic boundaries
Can be difficult to accurately assess
clinical extent
Inconsistencies
Omissions
24. Observer variability ( presence of nodal
disease and size measurement)
No inclusion of immunological status
Importance of extracapsular spread
N2 (bilateral involvement ) implies better
prognosis than N3 (large nodes greater
than 6 cm
25. The histologic grade is a qualitative
assessment of the differentiation of the
tumour expressed as the extent as to which a
tumour resembles the normal tissue at that
site
GX Grade cannot be assessed
G1Well differentiated
G2Moderately differentiated
G3 Poorly differentiated
G4Undifferentiated
26.
27. The National Cancer Institute (NCI), in
particular, defines biomarker as a:
“A biological molecule found in blood, other
body fluids, or tissues that is a sign of a
normal or abnormal process, or of a condition
or disease.
A biomarker maybe used to see how well the
body responds to a treatment for a disease or
condition. Also called molecular marker and
signature molecule."
28. Screening in general population
Differential diagnosis in symptomatic patients
Clinical staging of cancer
Estimating tumour volume
Prognostic indicator for disease progression
Detecting recurrences
Monitoring responses to therapy
Radioimmuno localization of tumour masses
Determining direction for immunotherapy
29. It should have high sensitivity and specificity.
It should have high positive and negative predictive
value.
It should be able to differentiate between neoplastic
and non-neoplastic disease and show positive
correlation with tumor volume and extent
It should predict early recurrence and have prognostic
value
It should be clinically sensitive, i.e. detectable at early
stage of tumor
Its levels should be preceding the neoplastic process,
so can be useful for screening
It should be easily assayable
35. This is significantly increased in OSCC
patients
Direct correlation with increasing staging
and nodal status
Measured with ELISA
Can be used as a good tool for prognosis
36. Ecological and observational studies
suggest that low serum albuminis
associated with higher mortality from
cancer.
Pre treatment serum albumin levels can
provide useful prognostic information in a
variety of cancers
37. Enzyme is found in the cells of almost all body
tissues
Anerobic condition:
PYRUVATE
LACTIC ACID
Increased LDH levels are due to increased
mitotic index and more lactic acid production by
tumor cells due to breakdown of glycoprotein
increased levels of serum LDH in patients with
OSCC and the levels correlated positively with
the clinical stage of the disease
LDH
38. Tumor proteins may induce the formation of
autoantibodies which can be detected in patient
serum.
Separate protein lysates from human SCC cell
lines, followed by Western Blotting using patient
sera.
Antigens are then identified using mass
spectrometry
Eg: Heat shock protein 70, sideroflexin 3
It has been suggested that these autoantibodies
might be used to establish effective new immune
therapies, besides using them for early diagnosis
of these tumors.
39. Antioxidant enzymes such as superoxide
dismutase and catalase can directly counter
balance the oxidant attack and may protect cells
against DNA damage.
Studies have shown that erythrocyte superoxide
dismutase activity was decreased in oral cancer
patients than in healthy individuals and patients
with oral lichen planus (OLP).
The low activity of erythrocyte superoxide
dismutase can be due to the depletion of
antioxidant defense system, occurring as a
consequence of overwhelming free radicals.
40. Keratins as tumor markers have two main applications:
In distinguishing epithelial from non-epithelial tumors
In distinguishing the type of epithelial tumor
The most obvious example is IL-1β whose values in saliva
were the highest of all the studied cytokines, while in serum its
values were below the level of detection.
It is shown that patients with oral cancer have significantly
higher concentrations of salivary IL-1β and IL-6 compared to
patients with leukoplakia and healthy individuals.
Increase in the concentrations of proinflammatory cytokines in
saliva might reflect the development of oral cancer from oral
leukoplakia.
Chronic inflammation constitutes one of the key risk factors
for OSCC. Studies indicate that IL-6–induced inflammation
promotes tumorigenesis in the oral cavity by altering global
LINE-1 hypomethylation.
41. The CD44 family of receptors includes multiple
variant isoforms, several of which have been linked
to malignant properties including migration,
invasion, and metastasis.
Expression of CD44 variant isoforms was
associated with advanced T stage (v3 and v6),
regional (v3) and distant (v10) metastasis,
perineural invasion (v6), and radiation failure (v10).
CD44 v6 and CD44 v10 were also significantly
associated with shorter disease-free survival
42. CD59 inhibits the complement membrane attack
complex by binding C5b678 and preventing C9 from
binding and polymerizing. It is present on “self” cells to
prevent complement from damaging them.
Tumor cells can escape complement-dependent
cytotoxicity (CDC) by expressing complement
restriction factors (CRFs), CD46, CD55, and CD59.
CD46, CD55, and CD59 were highly expressed in
HNSCC cells including T1/T2N0M0 stages.
The CRF expression was much lower or absent in
non-neoplastic squamous epithelia or in the
submucosa of both normal and tumor tissues.
43. IL-8 is an angiogenic chemokine with a
high expression level in the tumor tissues.
This plays important roles in developing
many human malignancies including
OSCC.
Results suggested that combination of
IL-8 gene polymorphisms and
environmental carcinogens might be highly
related to the risk of oral cancer.
44. Endothelins are 21-amino acid
vasoconstricting peptides produced primarily
in the endothelium, and have a key role in
vascular homeostasis.
Salivary endothelin-1 (ET-1) could be a good
biomarker for OSCC development in OLP
patients regardless of the degree of OLP
disease activity.
However, it appeared not to be a good
biomarker for detecting recurrence of OSCC
in patients in remission
45. also known as 90K, is a highly glycosylated,
secreted protein extensively studied in human
cancer, which binds galectin-1, galectin-3,
and galectin-7.
High expression levels of 90K are associated
with a shorter survival, the occurrence of
metastasis, or a reduced response to
chemotherapy in patients with different types
of malignancy
46. Tissue polypeptide antigen Tissue
polypeptide antigen (TPA), regarded as a
marker of cell proliferation, is a mixture of
fragments containing relatively stable
a-helical rod domains of simple
epithelium-type cytokeratins.
These fragments are probably released
during necrosis and lysis of the carcinoma
cells. TPA is known to be a sensitive, but
nonspecific tumor marker. Thus, TPA should
be regarded as a broad-spectrum epithelial
tumor marker
47. The possible correlation of TNF-a and -b
genes with the risk of oral cancer was
investigated in a study. The functional
polymorphisms TNF-a and TNF-b, which
affect gene expression, were investigated by
restriction fragment length polymorphism
analysis.
The frequencies of high-expression A2 TNF-a
allele and high expression B1 TNF-b allele
were significantly increased in cancer patients
compared to control.
48. To evaluate the usefulness of a tumor
marker, it is necessary to
Find reference values,
calculate predictive values,
evaluate distribution of marker values, and
determine the role of these values in
disease management
49.
50. Stell and Maran’s Head and Neck surgery and Oncology
AJCC cancer staging manual 6th Ed
Pocket Guide To TNM STAGING OF HEAD AND NECK
CANCER AND NECK DISSECTION CLASSIFICATION
Bhatt AN, Mathur R, Farooque A,Verma A, Dwarakanath B.S.
Cancer biomarkers - Current perspectives. Indian J Med Res
132, August 2010, pp 129-149
Cheng et al. A review of research on salivary biomarkers for
oral cancer detectionClinical and Translational Medicine 2014,
3:3
Choontharu MM, Binda A, Bhat S, Sharma SM. Role of tumor
markers in oral squamous cell carcinoma: Review of literature
and future consideration. SRM J Res Dent Sci 2012;3:251-6
Editor's Notes
CANCER, a malignant epithelial neoplasm, is a collective term for at least a hundred different diseases. These can be quite unique from the point of view of cause, histologic appearances, symptoms and prognosis. However, several common characteristic scan be seen:
Oral cancer is on the rise in our country and is one of the deadly cancers. The main causative factors are tobacco and alcohol
Tumor markers can be broadly classified based on the type of tissue as follows:
Increased serum LDH activity is considered as a marker of cellular necrosis, and serum LDH