EPIDERMOID CARCINOMA OF THE UTERINE CERVIXThe　 role of Proliferation Activity to the Histological Radiation Response

ABSTRACTS• Backgrounds. The result of radiation theraphy for epidermoid carcinoma of the uterine

cervix remains unsatisfactory. Among other factors, proliferation activity plays an important role to determine the success of radiation theraphy.

• Objectives. 1.To prove the proliferation activity of the epidermoid carcinoma of the uterine cervix plays an important role to determine the success of radiation theraphy. 2. To study cells proliferation activity of the epidermoid carcinoma of the uterine cervix before radiation theraphy both which has poor or good histological radiation response.

• Material and Method. Case control study is done, samples biopsies of epidermoid carcinoma of the uterine cervix was collected from patient in dr.Kariadi Hospital before radiation theraphy during the year 2000-2001. Case study group consisted of 33 samples which have poor histological radiation response, while the rest (33 samples) as control groups which have good histological radiation response. The degree of proliferation activity before radiation theraphy was examined using AgNOR staining method. The mean value of AgNORs of each group were analized using t-test and chi square test.

• Result. The profile patient differ unsignificantly between case study group and control group in term of age and degree o differentiation. The proliferation activity differs significanlt between poor histological radiation response group with good histological radiation response group (3,2567±0,652 vs 4,5594 ±0.6954 → p = 0,0001). Cut off point (COP) of 4 is based on receiver of curve calculation. Odds ratio is 16,7.

• Conclusion. It was found taht the proliferation activity of the poor patient with low proliferation activity (AgNORs droplet <4) than high proliferationa ctivity (AgNORs droplet ≥ 4). The chance was 16,7 times greater.

theoretical framework

Conceptual framework

SECTION 1: INTERNAL VALIDITY

1.1 The study addresses an appropriate and clearly focused on carsinoma serviks uteri’s proliferation activity that roles to radiation therapy

SELECTION OF SUBJECT1.2 The cases and controls are taken from

• Case: Cell proliferation activity levels before therapy in groups that has poor histology radiation response• Control: Cell proliferation activity levels before therapy in

groups that has good histology radiation respons1.3 The same exclusion criteria are not mentioned for both cases and controls. Selection of case and control samples is done randomly.1.4 Percentage of each group (cases and controls) participated in the study samples

• Cases: 33 samples (50%)• Control : 33 samples (50%)

1.5 Comparison is made Based on the histopathological assessment of radiation response in cervical biopsies after radiation therapy complete:

• Good radiation response: in biopsy not found many potent malignant cells, only malignant cells that already dead or degeneratived are found.

• Poor radiation response: in biopsy not only potent malignant cells but also died cells are found.

1.6 Cases are clearly defined and differentiated from controls1.7 It is clearly established that controls are non-cases

ASSESSMENT1.8 Measures are not mentioned to prevent knowledge of primary exposure influencing case ascertainment1.9 Exposure status is measured in a standard, valid and reliable way. The exposure such as proliferation activity of cell that define by granule AgNOR rate in 100 cell, it observed with light microscope with 1000x zoom:

• Low proliferation cell: granule<4• High proliferation cell: granule>4

CONFOUNDING

1.10 The main potential confounders are identified and taken into account in the design and analysis. Confounding variable such as age and cell differentiation of the patient in which the datas are taken from PA Log Book, medical record, and histophatological specimen. With result:

• In T test, the not signifficant age differencies from the patients p=0.612• In Chi-Square Test, the not significant levels of cell differencies p=0,082

STATISTICAL ANALYSIS1.11 Confidence intervals are not showned

SECTION 2: OVERALL ASSESSMENT OF THE STUDY

2.1 The study is nicely done (+) to minimize the risk of bias or confounding because confounding factor is added to be reconsidered in data analysis. The other factors already been in inclusion criteria. Sample with factor that not meet the requirement not included in the experiment.

2.2 Taking into account clinical considerations, your evaluation of the methodology used, and the statistical power of the study, we are certain that the overall effect is due to the exposure being investigated• Based on clinical considerations : According to the theory that immature cells that

grow rapidly (high proliferal activity) is a radiosensitive cells, in which the tumor is radiosensitive be destroyed by irradiation.

• Based on research methods: which is case control, with a view of causation between exposure (proliferative activity) and effects (radiological response).

• Based on statistical evaluation: Chi-square test obtained a meaningful relationship between cell proliferation activity before therapy in radiology good response group and poor radiological response with p = 0.0001.With odds ratio = 16.7, which means ECUC patients with low activity proliferation 16, 7 times more at risk of getting ugly radiological response than patients with high proliferation activity.

2.3 The results of this study is directly applicable to the patient group targeted by this guideline• Good radiological response shown in patients with epidermoid carcinoma

of the uterine cervix stage IIA-IV with high proliferative activity indicated by the number of AgNOR granules> = 4 on AgNOR staining of patient tissue biopsies

SECTION 3: DESCRIPTION OF THE STUDY

3.1 The study was funded by unknown. (Not mentioned in the experiment)3.2 Patients recruited from  1(parafin block archive: biopsy of cervix uteri epidermoid carcinoma in RSUP dr. Kariadi)3.3 The social setting of patients in the study are unknown (Not mentioned in the experiment)3.4 The criteria are used to decide who should cases

• Biopsy result of cervix uteri epidermoid carcinoma patients (3rd stadium)

• Only received complete external radiation therapy only with good histological radiation respond and high proliferation activity

• Hb >10 g%

3.5 The criteria are used to decide who should be controls:• Biopsy result of cervix uteri epidermoid carcinoma patients (3rd stadium)• Only received complete external radiation therapy only with poor

histological radiation respond and low proliferation activity• Hb >10 g%

3.6 The exposure or risk factor is investigated in the study:• Damage of cancer cells after radiation therapy• Cell proliferation activity:

• Cell cycle time• S-phase time• Volume doubling time• Mitotic Index• Growth fraction rate• S-phase fraction• G1-S-G2 fraction AgNOR coloring