1. Peresented by:Mohsen Koolivand MSc Clinical Of
Biochemistry
Molecular Mechanism Of Ovarian Cancer

2. Outline
 Introduction
 Risk factors
 Molecular Origin
The Molecular Of Mechanism
and Molecular Pathways
Guidelines

3. Introduction
Mohsen Koolivand MSc
Ovarian
Cancer
3–4% of cancer in women
estimated 22,000 new cases
Second most common gynecologic
malignancy
a disease of the postmenopausal
Early stage (I/II) detection has a survival
rate of over 90%
Symptoms are complex and often
misdiagnosed as other diseases
cellular and molecular characteristics,
identifying appropriate
block lymphatic vessels

4. Types Of Ovarian Tumors
The ovaries contain 3 main kinds of cells:
1. Epithelial
2. Germ cells
3. Stromal cells
Subsequently there are 3 main types of ovarian tumours:
1. Epithelial tumours
2. Germ cell tumours
3. Stromal tumours

5. Pelvic or abdominal pain
Symptoms
BloatingUrgent need to urinate
Frequent urination
abnormal menstrual cyclesSense of pelvic heaviness Back pain
Vaginal bleeding

6. Risk Factors
Family
History
Ethnicity Reproducti
on others

7. Family History
 The strongest risk factor
 A women with a single first-degree relative with ov.Ca has a relative
risk (RR) of approximately 3.6 for developing ov.ca compared with
general population
 The gene can be inherited through either the maternal or paternal
line, but has variable penetrance

8. Family History

9. Ethnicity
 Higher in white women
 Higher in north America and northern Europe
 BRCA1 and BRCA2 genes are more common among white women
of Ashkenazi descent
 Incidence of ov.ca is higher in countries with higher in countries with
higher per capita consumption of animal fat

10. Reproduction factors
 Nulliparous
 First childbirth after age 35 years
 Involuntary infertility
 Late menopause and early menarche
 Pts. With prolonged period or uninterrupted ovulation

11. Others
 Exogenous hormones :- HRT
 Dietary factors , Diets high in saturated animal fats seem to confer
an increased risk by unknown mechanisms …
# Japanese women who move to the United States have an
increased ovarian cancer risk.
<<<<<<<<<<<<<<<<

12. Protective Factors
 Multiparity: First pregnancy before age 30
 Oral contraceptives: 5 years of use cuts risk nearly in half
 Tubal ligation
 Hysterectomy
 Bilateral oopherectomy
 Lactation
 Epidemiologic and laboratory evidence suggest a potential role for
retinoids , vitamin D, NSAIDs as preventive agents for ovarian
cancer

13.  According to International Federation of Gynecology and Obstetrics
(FIGO) Staging of Ovarian Neoplasms :-
 Stage I. Growth limited to the ovaries
Ia —one ovary involved
Ib —both ovaries involved
Ic —Ia or Ib and ovarian surface tumor, ruptured capsule,
malignant ascites, or peritoneal cytology positive for malignant cells
Staging …

14. Staging …

15.  Stage II. Extension of the neoplasm from the ovary to the
pelvis
IIa—extension to the uterus or fallopian tube
IIb—extension to other pelvic tissues
IIc—IIa or b and ovarian surface tumor, ruptured capsule, malignant
ascites, or peritoneal cytology positive for malignant cells
Staging …

16. Staging …

17.  Stage III. Disease extension to the abdominal cavity
IIIa—abdominal peritoneal surfaces with microscopic metastases
IIIb—tumor metastases < 2 cm in size
IIIc—tumor metastases > 2 cm in size or metastatic disease in the
pelvic, paraaortic, or inguinal lymph nodes
Staging …

18. Staging …

19.  Stage IV. Distant metastatic disease
Malignant pleural effusion
Pulmonary parenchymal metastases
Liver or splenic parenchymal metastases (not surface implants)
Metastases to the supraclavicular lymph nodes or skin
Staging …

20.  molecular origins of cancer, such as ovarian cancer is influenced
by a complex signaling pathway.
 Ovarian cancer is also heterogeneous — multiple genetic and
epigenetic changes are evident in patients with ovarian cancer;
however, how such changes are selected for during tumorigenesis
is not yet clear.
Molecular Origin

24. Molecular Pathways
Ovarian cancer is also heterogeneous
— multiple genetic and epigenetic
changes are evident in patients with
ovarian cancer; however, how such
changes are selected for during
tumorigenesis is not yet clear.
Several genetic alterations cause of
high genetic instability in ovarian cancer:

25. Tumors ovariy
Proliferation
Apoptosis
Autophagy
Motility and invasion
Adhesion
Angiogenesis
characteristic

26. Sparc
SPARC Is a Key Regulator of Proliferation, Apoptosis and In
vasion in Human Ovarian Cancer
Secreted protein acidic and rich in cysteine (SPARC), a calcium-
binding matricellular glycoprotein, is implicated
in the progression of many cancers. investigations show
expression and function of SPARC in ovarian cancer.

27. PTEN
PTEN activity can also be lost through other
mechanisms such as epigenetic changes or post-
translational modifications or mutation .

28. BRCA1 and BRCA2
 BRCA1 and BRCA2 suggests that they are involved in two
fundamental cellular processes: DNA damage repair and
transcriptional regulation.

31. Tp53

33. KRAS
 RAS proteins are central mediators downstream of growth factor
receptor signaling and therefore are critical for cell proliferation,
survival, and differentiation.
 KRAS mutations are found in approximately 40% of patients with Type
I EOC tumors. In the majority of cases, these mutations are missense
mutations which introduce an amino acid substitution at position 12,
13, or 61. The result of these mutations is constitutive activation of
KRAS signaling pathways.

35. PI3K
 Activation of the PI3K pathway regulates:
 Cell growth
 Cell proliferation
 Cell survival
 The PI3K/Akt/mTOR pathway is frequently deregulated in OC
 The expression levels of both PIK3CA and phosphorylated Akt (pAkt) found to be associated
with decreased survival, and activation of the pathway, as measured by Akt or mTOR
phosphorylation levels