PROGNOSTIC MARKERS - I
Tumors of Breast, Colon & Liver
Features of Tumors which Influence Prognosis
1. Histologic types (Diagnostic classification). This is based
on histology, immunohistochemistry, electron microscopy,
cytogenetics, and molecular genetics.
2. Grading, usually on a scale of I to III, is based on the
degree of differentiation, the average number of mitoses per
high-power field, cellularity, pleomorphism, and an estimate
of the extent of necrosis (presumably a reflection of rate of
growth).
3. Staging. TNM stage of tumor represents the single most
important determinator of prognosis
4. Specific markers of tumors
Potential uses of tumor markers
1. Screening in general population
2. Differential diagnosis of symptomatic
patients
3. Clinical staging of cancer
4. Estimating tumor volume
5. As a prognostic indicator for disease
progression
6. Evaluating the success of treatment
Prognostic Markers Of Breast
Cancer
Estrogen and progesterone receptors
• Positive cases have slightly better prognosis and good
response to therapy
• ER + PR +
80% Response to treatment
• ER + PR 25 – 45 % response
• ER - PR 10 % response
Prognostic Markers Of Breast Cancer
HER2/neu.
• overexpression of this oncogene as determined either
by immunohistochemistry or FISH is an excellent
predictor of response to trastuzumab
• Although it identifies a subset of patients with poor
prognosis, particularly when lymph node metastases
are present
Prognostic Markers Of Breast Cancer
BRCA1 protein expression.
• Absent or reduced nuclear BRCA1 expression as
measured immunohistochemically is associated with
several microscopic unfavorable features and a
shorter disease-free interval,
• The cytoplasmic expression of this marker seems
associated with the development of tumor recurrence
Prognostic Markers Of Breast Cancer
P53 and nm23.
• Accumulation of P53 protein (presumably as a result of
gene mutation) and low expression of the nm23 protein
have been said to correlate with reduced patient survival.
COX2
• Expression of cyclooxygenase 2 (COX2), a molecule
linked to neovascularization and tumor growth, has been
found to be associated with poor prognostic markers in
one study
Breast Carcinoma - Prognosis
Better prognosis
Bad prognosis
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Tumor insitu
Size less
Lymph node metastasis less
No Distant metastasis
Histologic grade well diff.
Histologic type
Tubular, mucinous,
medullary
• ER PR positive
• HER 2 / NEU Expression
less
Infiltrating tumor
More
More number of nodes
Present
Poorly differentiated
• Ductal
• Negative
• Over expression
PROGNOSTIC MARKERS FOR COLON CANCER
1. Tumor size
2. Microscopic tumor type: (Mucinous carcinoma, signet
ring carcinoma, and anaplastic carcinoma have a worse
prognosis than the ordinary type of adenocarcinoma)
3.
4.
5.
6.
Microscopic grade
Local extent
Lymph node involvement.
Staging. The staging systems, which represent a
combination of the criteria of local extent (and lymph
node involvement) have proved to be a powerful way
of predicting the prognosis of patients with colorectal
carcinoma
PROGNOSTIC MARKERS FOR COLON CANCER
7. Age. Tumors occurring in very young and very old
patients are associated with a poor prognosis
8. Sex. The prognosis is significantly better for females
than for males
9. CEA serum levels. Elevated serum CEA levels
>5.0 ng/mL have been shown to have an adverse
impact on prognosis
10. Tumor location. In one large study, lesions located in
the left colon had the most favorable prognosis,
whereas those situated in the sigmoid colon and
rectum had the worst outcome
PROGNOSTIC MARKERS FOR COLON
CANCER
11. Obstruction. This feature has been found to be an
indicator of a worsened prognosis
12. Perforation. Perforation resulting from extensive
tumor invasion of the bowel wall is linked to a poor
prognosis
13. Tumor margins and inflammatory reaction.
Carcinomas having pushing margins and an
inflammatory infiltrate at the interphase between the
tumor and the neighboring tissue have a better
prognosis than those lacking these features
PROGNOSTIC MARKERS FOR COLON
CANCER
14. Tumor budding. This feature, which is defined as the
presence of isolated tumor cells or clusters of >5 cells
at the invasive tumor front, has emerged as a strong
and independent prognostic marker of poor outcome
15. Vascular invasion : When vein invasion is
present,there is a significant increase in the incidence
of distant metastases
16. Perineurial invasion: unfavorable pathologic findings
PROGNOSTIC MARKERS FOR COLON CANCER
17. Mucin-related antigens. Colorectal carcinomas that
express the mucin-associated antigens sialyl-Tn and
sialyl-Lewis(x) antigen have been said to run a more
aggressive clinical course
18. Fascin. High fascin expression as detected
immunohistochemically has been related to
diminished survival
PROGNOSTIC MARKERS FOR COLON CANCER
19. Claudin-1. Loss of this tight junction-associated
protein is said to be a strong predictor of disease
recurrence and poor patient survival in stage II
colonic cancer
20. BCL2 protein expression. It has been stated that
immunohistochemical expression of BCL2 is
associated with an improved prognosis
PROGNOSTIC MARKERS OF LIVER CANCER
1. Stage. This constitutes the most important prognostic
determinator
2. Size. In most series, patients with ‘small’ tumors
(from 2 to 5 cm in diameter) had a significantly better
prognosis
3. Encapsulation. The liver cell carcinomas that are
totally surrounded by a capsule behave in a less
aggressive fashion than those lacking this feature
4. Number of tumors. Single lesions are associated with
a better survival rate than multiple tumors
PROGNOSTIC MARKERS OF LIVER CANCER
5. Portal vein involvement. This finding constitutes an
important adverse prognostic sign
6. Microscopic type. The fibrolamellar variant is
associated with a definitely better prognosis
7. Microscopic features. The microscopic features that
proved to be independent predictors of survival were
vascular invasion, high nuclear grade, and mitotic
activity
8. Presence of cirrhosis. Carcinomas associated with
cirrhosis have a worsened prognosis
PROGNOSTIC MARKERS OF LIVER CANCER
9. Serum AFP levels. High AFP levels at presentation
are said to have not only a diagnostic but also an
adverse prognostic significance
10. CMYC amplification. It has been stated that the
presence of this feature in hepatocellular carcinoma
predicts an unfavorable prognosis
11. P-glycoprotein. In one study, the chemotherapy
response of hepatocellular carcinoma was inversely
related to Pgp expression, the difference being
statistically significant