This document discusses cyclinD1 and its role as a marker for oral cancer progression. It finds that cyclinD1 expression increases from normal epithelium to leukoplakia to oral squamous cell carcinoma. Higher cyclinD1 expression correlates with poorer tumor differentiation and worse patient outcomes like early death or recurrence. The study concludes that cyclinD1 overexpression may help identify high-risk oral cancer patients and serve as a prognostic marker.

1. CyclinD1-a luminary marker for
progression of carcinogenesis
Dr.Reena Rachel John
Vinayaka Missions Sankarachariar Dental College and Hospital
Salem
CyclinD1 – a luminary marker
for progression of
Carcinogenesis
ACADEMIC WRITING
Prof. Dr. Reena Rachel John
Vinayaka Missions Sankarachariar Dental College and Hospital (VMRF DU)
Salem – Tamilnadu
Application no . bfeadd47e72f11e98857bd5fd00aa9e7
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2. INTRODUCTION
Oral cancer remains a significant health burden worldwide.
Oral cancer forms 4% of malignancies in the West and 40% of all
cancers in the Indian subcontinent.
Oral cancer is the sixth most common human cancer.
Five year mortality rate is 50%.
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3. According to statistics, the number of deaths in India in 2012
due to oral cancer was 36463 males and 15361 females
Varshitha . A/J. Pharm. Sci. & Res. Vol. 7(10), 2015, 845-848
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4. Since published data is full of evidence that CyclinD1 is an important
marker for OSCC. This study was directed at finding if there is indeed a
correlation between cyclind1 expression and clinicopathological
parameters of oral cancer.
Excessive cell proliferation which leads to Cancer can be a result of
disruption in cell signalling , cell cycle and the mechanism to repair cell
damage or elimination of dysfunctional cells .
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5. Protein encoded by CCND1 gene is
located on the long arm of
chromosome 11(band 11q13).
The overexpression of cyclin D1 has
been linked to the development and
progression of cancer.
Deregulated cyclin D1 degradation
appears to be responsible for the
increased levels of cyclin D1 in several
cancers.
What is CyclinD1?
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6. The ability of these cyclins to activate the cyclin
dependent kinases (CDK4 & CDK6) is the most
extensively documented mechanism for their
oncogenic actions and provides an attractive
therapeutic target.
The role of CyclinD1 as a prognostic marker still
remains controversial.
*Perisanidis C,PerisnidisB,WrbaF,Brandstetter A,ElGazzarS,PapadogeorgakisN et al, Evaluation of
immunohistochemical expression of p53,p21,p17,cyclinD1,Ki67 in oral and oropharyngeal squamous cell
carcinoma.J Oral Pathol Med 2012;41:40-6. CC BY-SA-NC

7. Purpose of the study
This study was undertaken to see the expression of Cyclin D1 in oral
squamous cell carcinoma and to correlate its expression with age, sex,
site, associated habits, TNM staging, histological differentiation and
follow up status.
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8. Methodology
• Oral Cancer cases – 49 ----17 females,32 males; age 34yrs –80 yrs
(mean 51 yrs)
• PMD cases – 20 ---- 5 females,15 males ; age 26yrs – 70 yrs
(mean 50 yrs)
• Control – 11 ---- 4 females ,7 males ; age 26 yrs –78 yrs
(mean48 yrs)
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9. 97.95% cases had associated habit of tobacco chewing / beedi
smoking of an average period of 15years.
80% of the Oral cancer cases presented at Stage 4.
Most common site involved was
• Buccal mucosa(44%),
• Retromolar trigone(25%),
• Maxilla(17%) ,
• Mandible(7%),
• Tongue (4%),
• Floor of mouth(3%).
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10. METHODOLOGY
Informed Consent taken . IEC approval obtained from SRU and VMU.
Incisional biopsy was done.
Histopath. grading done of the H & E stained sections.
IHC study carried out using polymer labelling technique
(Dako,Envision)
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11. Presence of brown coloured end product at the site of target antigen
was indicative of positive immunoreactivity . Absence of staining was
considered negative.
In every slide , positive tumor cells per hotspot was calculated and
mean percentage per slide (labelling index) was determined.
Labelling score of 1, 2,3,4 was assigned for labelling indices 1-25%,
26-50% , 51-75% and >75% respectively.
All the relevant clinical , histopath and IHC data was tabulated and
subjected to appropriate statistical analysis.
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12. T4N1Mx, Histopath – MDSCC , IHC - Score 3
Treatment done – Surgery, Follow up status – Alive without disease 28 mths
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13. Grading of oral
cancer
Cyclin D 1 scoring P value
Negative Score 1 Score 2 Score 3 Score 4
WDSCC 4 5 5 2 1 0.738
MDSCC 1 2 3 7 6 0.0281
PDSCC 0 0 0 0 1 0.001
Veruccous
Carcinoma
0 1 2 0 0 0.0712
Table 3: Grading of Oral cancer and Cyclin D1 scoring among the Oral Cancer Patients
P value derived by Chi-square test
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14. 20 of the 49 cases were managed by Surgery +/- RT +/- CT and
were followed up for a period ranging from 3 months to 42
months.
• Alive without disease – 11 ( CyclinD1 Score 1-3)
• Alive with disease – 2 ( Cyclin D1 Score 4)
• Dead following treatment - 7 ( Cyclin D1 Score 3/4)
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15. Follow-up
status
Cyclin D1 scoring P value
Negative Score 1 Score 2 Score 3 Score 4
Alive with
recurrence
0 0 0 0 2 .0178
Alive
without
disease for
more than
12 months
2 2 5 1 1 0.0265
Dead 3 -6
months
after
treatment
0 0 0 3 4 <.0001
Not treated 0 4 4 5 5 0.375
Table 4: Cyclin D 1 scoring and the follow-up status of Oral Cancer Patients
P value derived by Chi-square test
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16. Discussion
• Strong expression of CyclinD1 in PMD cases in our study was 31.57%.
This increased expression indicates the obvious role of CyclinD1 in
carcinogenesis.
• In our series , CyclinD1 expression was seen in the basal and
parabasal layers in leukoplakia without dysplasia. Erythroplakia and
Leukoplakia with dysplasia showed CyclinD1 overexpression
extending beyond the spinous cell layer.
This is evidence that a PMD with CyclinD1 expression extending into
the spinous layer indicates Carcinogenesis.
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17. • CyclinD1 overexpression was seen in 65.85% of Oral cancer cases
similar to Shintani et al. CyclinD1 overexpression frequencies were reported
ranging from 17.1% to 83% in OSCC.
*Kaminagakura E,Werneck DaCunha I,Soares FA,Nashimoto IN,KowalskiLP.CCND1 amplification and protein overexpression
in Oral Squamous Cell Carcinoma of young patients. Head Neck 2011;33:1413-1419.
• Labelling index showed correlation with histopath grading . PDSCC and MDSCC
showing Score 4. Angadi and Krishnapillai and Mishra and Das noted an
uniformly increasing intensity in relation to histopath differentiation while
Castle et al found no correlation.
*P.V.Angadi and R. Krishnapillai, CyclinD1 overexpression in Oral Squamous cell carcinoma and Verrucous
Carcinoma:correlation with histological differentiation.Oral Surgery Oral Medicine Oral Pathology Oral Radiology and
Endodontology2007;103(3):30-35.
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18. Age, gender,site , stage showed no correlation with CyclinD1 overexpression in
our study unlike Haas et al who found a significant correlation with risk of
recurrence in tongue ca with CyclinD1 overexpression.
Haas S , Hormann K et al .Expression of cell cycle proteins in Head and Neck cancer correlates with tumor site rather than
tobacco use. Oral Oncol 2002;38:618-623.
Follow up status – 9 patients had score 3 and 4 who showed either recurrence or
was dead within 3-6 months following treatment.
This indicates that Cyclin D1 is a potential prognostic marker.
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19. NORMAL EPITHELIUM TO CARCINOGENESIS
H&E
NORMAL
H&E
LEUKOPLAKIA
WITHOUT
DYSPLASIA
H&E
LEUKOPLAKIA
WITH
DYSPLASIA
H&E
OSCC
BASAL
IHC 40x
SPINOUS
IHC 40x IHC 40x
BASAL & PARABASAL
IHC 40x
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20. CONCLUSION
 Cyclin D1 is a luminary marker.
 Cyclin D1 may be used as an indicator to predict recurrence.
 Cyclin D1 may be a prognostic marker which may help in identifying
subgroups of Oral Cancer with poor prognosis.
 The observations in this field may contribute significantly to the
patient well-being and decrease morbidity and mortality by
establishing Cyclin D1 as a prognostic marker.
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21. ACKNOWLEDGEMENT
ACADEMIC WRITING
Department of Oral and Maxillofacial Surgery , VMSDC and Hospital
Salem, VMRF DU.
Department of Oral and Maxillofacial Pathology , Faculty of Dental
Sciences, SRIHER DU.
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