Download - Analysis of salivary secretor status in patients with oral submucous fibrosis: a case-control study
ORIGINAL ARTICLE
Oral Pathology
Analysis of salivary secretor status in patients with oralsubmucous fibrosis: a case-control studyKaveri Hallikeri1, Ravichandra Udupa1, Krutika Guttal2 & Venktesh Naikmasur2
1 Department of Oral and Maxillofacial Pathology, Sri Dharamasthala Manjunatheshwara College of Dental Sciences & Hospital, Dharwad,
Karnataka, India
2 Department of Oral Diagnosis and Radiology, Sri Dharamasthala Manjunatheshwara College of Dental Sciences & Hospital, Dharwad,
Karnataka, India
Keywords
blood group, carcinoma, oral submucous
fibrosis, saliva, secretor status.
Correspondence
Dr Kaveri Hallikeri, Department of Oral and
Maxillofacial Pathology, S.D.M. College of
Dental Sciences and Hospital, Sattur
Dharwad, Karnataka 580009, India.
Tel: +91-0836-2468142
Fax: +91-0836-2467612
Email: [email protected]
Received 11 October 2013; accepted 4 March
2014.
doi: 10.1111/jicd.12100
AbstractAim: Many individuals have various tobacco-related habits, yet only some
develop clinical manifestation of lesions. This raises the question of whether
there any inherent or host risk factors involved in the pathogenesis which need
to be further investigated. The aim of the present study was to analyze the
ABO antigen, secretor status, and blood groups of patients.
Methods: The study consisted of 99 participants, with 33 patients allocated to
three groups: (a) patients with a tobacco-related habit and oral submucous
fibrosis (OSF); (b) patients with a tobacco-related habit, but no lesions; and
(c) healthy controls. A total of 1 mL unstimulated saliva was collected in a
sterile test tube, and the Wiener agglutination test was performed to analyze
the ABO antigen in all three groups.
Results: All of the OSF patients were non-secretors, whereas 84.8% were non-
secretors in the group of individuals with habits as compared to 15.2% in the
healthy group. A statistically-significant difference was observed between the
OSF and healthy groups. The patients in the OSF group were predominantly
blood-group A, followed by groups O, B, and AB.
Conclusion: There is a correlation between salivary secretor status and the
development of OSF. Thus, non-secretors are at greater risk of and more prone
to the development of oral lesions. Blood-groups A and O predominate over
the B and AB blood groups.
Introduction
Oral submucous fibrosis (OSF) is a high-risk precancer-
ous condition related to chewing areca nut alone or as a
component of betel quid. Approximately 600 000 000
people worldwide chew raw areca nut or in any processed
form.1 In India, there is increasing addiction tendency
among young people due to easy access of tobacco prod-
ucts, effective price changes, and marketing strategies.
There are numerous commercially-prepared areca nut
preparations, and gutkha is the most popular. Recent epi-
demiological data indicate that the number of OSF cases
has increased rapidly in India from an estimated 250 000
cases in 1980 to 2 000 000 cases in 1993.2 This disease
has become a major public health issue in India, owing to
its prevalence among 20–30 year olds, and its association
with malignant transformation.
OSF is an irreversible condition; once developed there is
no effective treatment. The malignant transformation rate
associated with OSF ranges from 7% to 13%.3 More than
2400 new cases of oral cancer arising from OSF are diag-
nosed every year in Taiwan due to the prevalent use of
betel quid.4 Jian et al.5 analyzed the clinical symptoms and
signs in 29 cases of OSF cases, which transformed
into squamous cell carcinoma. Andakumar et al. and
Ko et al.6,7 reported a malignant transformation rate of
4–30.4% in India and 12.28% in Taiwan, respectively. Recent
data show that the potential of malignant transformation
ª 2014 Wiley Publishing Asia Pty Ltd 1
Journal of Investigative and Clinical Dentistry (2014), 5, 1–6
in OSF is much higher compared to other premalignan-
cies.8 Therefore, early diagnosis of this potentially-malig-
nant oral lesion is essential for better prognosis.
Although biopsy is the gold standard to observe the
earliest changes in the epithelium of premalignant lesions,
repeat biopsies might not be feasible. To overcome these
problems, the salivary secretor status would be useful. It
has been reported that non-secretor individuals are more
prone to develop lesions, and certain types of cancers are
more prevalent in particular blood-group types. Various
authors have shown the relationship between the patho-
genesis of disease and secretor status, which is a possible
factor influencing disease status.9,10 A higher intensity of
oral disease is found among non-secretors in terms of
precancerous and cancerous changes to tissues of the oral
cavity. Oral disease susceptibility is reflected in the occur-
rence of epithelial dysplasia, which was found almost
exclusively in the non-secretor group. The presence of the
epithelial antigen has a protective role in infections by
interfering with the binding sites either on the surface of
microorganisms or to epithelial cells. Studies have shown
that infection is more common in non-secretors.11,12 It
has also been reported that individuals with blood-group
A have a predisposition for oral cancer. The functional
loss of the A enzyme in dysplasia and carcinoma has been
reported, whereas in normal epithelium it is strongly
positive. This is due to the downregulation of glycosyl-
transferase, which is involved in the biosynthesis of A and
B antigens, and is associated with tumor development.13
Based on this, the present study was undertaken in order
to determine secretor status and blood group in OSF
patients and those with a tobacco-related habit without
lesions, and healthy controls.
Materials and methods
Salivary secretor status was studied in 99 individuals; each
group consisted of 33 patients: (a) patients with a
tobacco-related habit and OSF (group I); (b) patients
with a tobacco-related habit, but no lesions (group II);
and (c) healthy controls (group III).
Establishing secretor status in saliva
The methodology followed for assessment was adapted
from Vidas et al.14 A total of 1 mL non-stimulated saliva
was collected from each patient and stored in a sterile
glass vial. The saliva was then poured into a sterile test
tube and closed with a lid. The test tube was then placed
in boiling water bath for approximately 10 min to destroy
enzymes. The supernatant fluid was then extracted by a
centrifugal force of 1700 turns in 10 min. The Wiener
agglutination test was used to establish secretor status.
The test serum was diluted in a salted physiological solu-
tion of 1:10 dilution. The following antiserum was then
placed into test tubes marked I–IV: (a) I, one drop of sal-
iva + one drop of antiB serum; (b) II, one drop of saliva
+ one drop of antiA serum; (c) one drop of physiological
solution + one drop of antiB serum; and (d) one drop of
physiological solution + one drop of antiA serum.
After 10 min at room temperature, one drop of 2–3%of suspension A erythrocytes was added into sterile tubes
II and IV, and one drop of suspension B erythrocytes into
tubes I and III. All the test tubes were agitated, and left at
room temperature. Readings were available after 1 h. Test
tubes III and IV (controls) showed agglutination. Aggluti-
nation in tube I was as a result of the presence of sub-
stance A2 in saliva, that is, of secretor A, while the
agglutination in tube II was proof of secretor B. The
absence of agglutination in tubes I and II designated AB
secretor, and at the same time, agglutination in tubes I
and II confirmed that the person was a non-secretor.
Results
The type and distribution of tobacco-related habits and
the detailed percentages among the study groups are out-
lined in Table 1. The percentage of secretor status among
patients with a tobacco-related habit and OSF (group I),
patients with a tobacco-related habit, but no lesions
(group II), and healthy controls (group III) is shown in
Figure 1. All of the patients in group I were non-secre-
tors, whereas in group II, 84.8% were non-secretors com-
pared to 15.2% in group III. A statistically-significant
difference was observed between groups I and III. The
correlation of duration and intensity of habits with secre-
tor status could not be done due to the large difference
in secretor status among the individuals in group II (cor-
relation requires at least equal distribution of secretor sta-
tus among the study group). Details of the association
between study groups and blood-group type is shown in
Table 2. It was also observed that OSF was more preva-
lent among those with blood-group A (36.36%) com-
pared to groups O (33.33%), B (27.27%), and AB
(3.03%).
Table 1. Type of tobacco-related habit and distribution percentage
among the study groups
Habits OSMF group % Habit group % Total
Areca nut 4 12.12 5 15.15 9
Gutkha 20 60.61 6 18.18 26
Pan masala 2 6.06 3 9.09 5
Combination 7 21.21 19 57.58 26
Total 33 100 33 100 66
OSMF, oral submucous fibrosis.
2 ª 2014 Wiley Publishing Asia Pty Ltd
Salivary secretory status K. Hallikeri et al.
Discussion
The prevalence rate of OSF in India ranges from 0.2% to
1.2%. Individuals between 20 and 40 years of age are
most commonly affected, but individuals aged between 2
and 89 years have also been reported to be affected.2 In
the present study, OSF was more prevalent in the second
decade of life, and was found to be strongly associ-
ated with a gutkha habit (20/33) of 1–10 years. Gutkha
chewing is a popular habit, with potential links to the
occurrence of oral cancer.15 Other tobacco-related habits
included betel nut chewing (4/33), pan masala (2/33),
and mixed habits (7/33).
The components of gutkha, such as areca nut extract,
are known to induce mutagenic and genotoxic effects, in
addition to inducing preneoplastic, as well as neoplastic
lesions of the oral cavity. Reactive oxygen species pro-
duced during auto-oxidation of areca nut polyphenols are
crucial in the initiation and promotion of oral cancer.16
The development of disease in patients with tobacco-
related habits is unpredictable. Inherent or host risk fac-
tors are most likely responsible for the development of
OSF. A detailed analysis of these factors is required to
assess the cause of lesion development in individuals with
tobacco-related habits. Based on this, in the present study,
we determined the secretor status in the above-mentioned
groups.
A secretor is defined as a person who secretes their
blood-type antigens into body fluids, such as saliva in the
mouth and mucous in the digestive tract and respiratory
cavity. A non-secretor puts little or none of their blood
type into these same fluids.14 The blood-group antigens
are genetically regulated by A, B, and H levels and secre-
tor genes, and subsequently, blood-group antigens are
expressed on erythrocytes and oral epithelial cells. These
cell surface carbohydrates are involved in cell-to-cell and
cell-to-substrate interactions, and changes in cell surface
carbohydrates are reflected in cellular behavior.13 The
non-secretor status of a patient could influence the devel-
opment of systemic and oral manifestations.
The ability to secrete blood-group antigens plays an
important role in the natural resistance of organism to
infection. Increased susceptibility to microbial infection
and a higher occurrence of urinary tract infection have
been reported in non-secretor individuals.17–19 Clark
et al.18 reported that non-secretors of the ABO group
antigen have an increased risk of developing peptic ulcers,
increased susceptibility to microbial infection, and a
higher occurrence of urinary tract infections. The ability
to secrete blood-group antigens plays an important role
in the natural resistance of organisms to infection. In a
study of 100 cases of leukoplakia, most of the non-secre-
tors were in the diseased group. Oral candidiasis among
non-secretors is also frequently. The non-secretor status
facilitates the prolonged candidal adhesion to mucosal
sites.20
In the present study, all the individuals in group I were
non-secretors; 84.8% of the individuals in groups II were
non-secretors and 15.2% were secretors. In contrast,
84.8% of the individuals in group III were secretors, and
only 15.2% were non-secretors.
We hypothesize that non-secretors might have an
added effect in the pathogenesis OSF, as all of the OSF
patients were non-secretors, and non-secretor individuals
with a tobacco-related habit are more likely to be prone
Table 2. Blood groups among the study groups
Blood OSMF group % Habit group % Control group % Total %
A 12 36.36 14 42.42 17 51.52 27 27.27
B 9 27.27 8 24.24 10 30.30 43 43.43
AB 1 3.03 2 6.06 4 12.12 7 7.07
O 11 33.33 9 27.27 2 6.06 22 22.22
Total 33 100.0 33 100 33 100 99 100.00
OSMF, oral submucous fibrosis.
Figure 1. Secretor status among the study groups. Group I, patients
with a tobacco-related habit and oral submucous fibrosis; group II,
patients with a tobacco-related habit, but no lesions; and group II,
healthy controls. ( ) Non Secretor; ( ) Secretor.
ª 2014 Wiley Publishing Asia Pty Ltd 3
K. Hallikeri et al. Salivary secretory status
to developing oral lesions. These patients would require
regular follow up to diagnose the disease as early as possi-
ble to provide the best treatment. To the best of our
knowledge, there have been no published studies compar-
ing secretor status in individuals with tobacco-related
habits; thus, ours is the first to estimate secretor status in
these individuals. Previous studies have correlated secretor
status and the severity of the disease, as in leukoplakia.21
Secretor status is well documented in oral cancer and pre-
malignant lesions, such as like leukoplakia, and fungal
infections, such as candidiasis.11,22 Vidas et al.14 studied
the secretor status in patients with pathological changes
of the oral mucosa in lichen ruber planus, erosivos, and
leukoplakia. Of the 61 patients, only 15 subjects were
non-secretors. The patients with a non-secretor status had
severe degree of the disease, whereas a mild degree of the
disease was recorded for the secretors. Secretor status has
been linked to the potentially-malignant oral lesions of
candidal leukoplakia; the non-secretor status facilitates
the prolonged adhesion of Candida to the mucosa, and in
addition, epithelial dysplastic changes seen exclusively in
non-secretors.23 The prevalence of Candida in OSF has
been reported to range from 40% to 63.6%, with Candida
albicans the predominant species isolated. These carry sig-
nificant risks of malignant transformation. The non-secre-
tor saliva not only fails to prevent attachment of Candida,
but also promotes the binding of Candida to tissue. With
potentially-malignant disease, the superadded candidal
infection needs special attention, as it is postulated that
nitrosamine compounds produced by Candida species
might directly, or together with other chemical carcino-
gens, activate specific proto-oncogenes, and thus facilitate
the development of malignant lesion.24–26 Cervoic et al.
studied the presence of the ABO antigen in the saliva of
patients with oral cancer, and found that 12 of 57
patients were non-secretors of blood-group antigens in
saliva. There was no significant difference between the
experimental and control groups.23
The interesting molecular basis is that epithelial cells in
non-secretors do not have an active flucosyl-transferase,
the activity of which is associated with the expression of
the ABO blood-group oligosaccharides. Human carci-
noma colon cell line has shown the loss of AB glycosyl-
transferse, which can enhance the malignancy of the cell
lines. Molecular studies of bladder cancer have shown
that the loss of expression of A-transferase is related to
the loss of chromosome at 9q34, which is a locus for the
ABO gene.27
The distribution of ABO blood groups in and around
Bangalore has been reported to be 9.81% for the O
group, 29.95% for the B group, 23.85% for the A group,
and 6.37% for the AB group.28 The South Indian study
by Das et al.29 showed that group O is the most predom-
inant, followed by groups B and A. Another South
Indian study, conducted in the Chittoor district of And-
hra Pradesh, India, also showed a similar pattern of
blood-group distribution.30 In the present study, it was
also observed that OSF was prevalent in patients with
blood-group A (36.36%), followed by groups O
(33.33%), B (27.27%), and AB (3.03%); however, these
correlations were not statistically significant. There are no
data available regarding the blood group and incidence
of OSF occurrence in these individuals. The present study
is a pilot study and the first of its kind to correlate secre-
tor status in individuals with OSF. However, future stud-
ies with larger sample sizes are required to confirm the
present findings.
The deletion of blood-group antigen A from premalig-
nant oral mucosal lesions is regarded as an example of
impaired synthesis of cell surface carbohydrates associated
with malignant change. This is due to the accumulation
of precursors or carbohydrates, that is, a H antigen in
premalignant lesions. The loss of the A antigen with the
accumulation of the H antigen suggests that the activity
of enzymes, which converts the H antigen to A, decreases
in premalignant lesions. In an immunohistochemistry
study, it was revealed that the H antigen accumulates in
the cell membrane of premalignant lesions with dysplasia,
and is irregularly distributed in oral squamous cell carci-
noma. This difference in distribution can be beneficial for
the early detection of cancer.21,31 Bryne et al.32 reported
that the loss of H-antigen expression at the invasive front
was well correlated with tumor development and the his-
tologic grade of tumor malignancy, rather than H-antigen
staining in the entire tumor.
In a prospective study by Lamey et al.,33 which
included 100 Sri Lankan patients with oral cancer and
controls, secretor status appeared to be an associated risk
marker for the development of lesions. In a hospital-
based study by Jaleel et al., blood groups were recorded
in oral cancer patients. It was concluded that people
with blood-group A were 1.46 times at a greater risk of
developing oral carcinoma, followed by those with
blood-groups B, AB, and O.12 There are various studies
reporting that individuals with blood-group A are prone
to developing carcinomas. In their studies, Raghavan
et al. and Toto and Nadimi34,35 also reported the
increased susceptibility of blood-group A to oral cancer.
Conclusion
Non-secretor status in an individual with a tobacco-
related habit indicates that there is alteration in the epi-
thelial surface carbohydrates, which marks the changes
in the epithelium and makes oral mucosa prone to dis-
ease development. The present study demonstrated that
4 ª 2014 Wiley Publishing Asia Pty Ltd
Salivary secretory status K. Hallikeri et al.
non-secretor individuals with a tobacco-related habit
developed oral lesions, thus patients with a history of
betel quid or areca nut habits in any form can be con-
sidered to be at risk. Secretor status can be part of rou-
tine investigations to assess the disease status and
whether an individual’s susceptibility manifests the dis-
ease. There is a need to analyze which particular groups
of individuals are more prone to develop OSF using
larger sample sizes.
Acknowledgments
The authors would like to thank Mrs Ambika Patil (Sri
Dharamasthala Manjunatheshwara College of Dental Sci-
ences & Hospital, Dharwad. Karnataka, India) for her assis-
tance in examining the salivary secretary status, and Dr
Arvind M. Yeri (Sri Dharamasthala Manjunatheshwara Col-
lege of Dental Sciences & Hospital, Dharwad. Karnataka,
India) for permitting us to utilize the laboratory facilities.
References
1 Gupta PC, Warnakulasuriya S. Global
epidemiology of areca nut usage.
Addict Biol 2002; 7: 77–83.2 Ranganathan K, Umadevi M, Joshua
E, Kirankumar K, Saraswathi TR. Oral
submucous fibrosis: a case control
study in Chennai South India. J Oral
Pathol Med 2004; 33: 274–7.3 Tilkarartne WM, Klinikowski MF,
Saku T, Peters TJ, Warnakulasuriya S.
Oral submucous fibrosis: review on
aetiology and pathogenesis. Oral On-
col 2006; 42: 561–8.4 Li N, Jian X, Hu Y, Xu C, Yao Z,
Zhong X. Discovery of novel biomar-
kers in oral submucous fibrosis by
microarray analysis. Cancer Epidemiol
Biomarkers Prev 2008; 17: 2249–59.5 Jian XC, Shen ZH, Liu SF. Oral sub-
mucous fibrosis-case reports. J Clini-
cal Stomatol 1985; 1: 12–3.6 Andakumar A, Thimmasethy KT,
Sreeramareddy NM. A population-
based case-control investigation on
cancers of the oral cavity in Banga-
lore, India. Br J Cancer 1990; 62: 847–51.
7 Ko YC, Huang YL, Lee CH. Betel
quid chewing, cigarette smoking and
alcohol consumption related to oral
cancer in Taiwan. J Oral Pathol Med
1995; 24: 450–3.8 Gupta MK, Mhaske S, Ragavendra
R, Imtiyaz. Oral submucous fibrosis
—current concepts in etiopathogene-
sis. People’s J Sci Res 2008; 1: 39–44.9 Sheinfield J, Shaeffer AJ, Cordon-
Cordo C, Rogatko A, Fair WR.
Association of Lewis blood group
phenotype with recurrent urinary
tract infections in women. N Engl J
Med 1989; 320: 773–7.
10 Lomberg H, Hollstrom J, Jodal U,
Svanborg-Eden C.. Secretor status
and renal scarring in girls with recur-
rent pyelonephritis. Microbiol Immu-
nol 1991; 35: 371–4.11 Lamey PJ, Darwazeh AM, Muirhead
J, Rennie JS, Samaranayake LP,
MacFarlane TW. Chronic hyperplastic
candidosis and secretor status. J Oral
Pathol Med 1991; 20: 64–7.12 Jaleel BF, Nagrajappa R. Relationship
between ABO blood groups and oral
cancer. Indian J Dent Res 2012; 23:
7–10.13 Dabelsten E, Gao S. ABO blood
group antigens in oral cancer. J Dent
Res 2004; 84: 21–8.14 Vidas I, Delajlija M, Temmer-Vuksan
B, Stipeti�c-Mravak M, Cindri�c N,
Maric�ı�c D. Examining the secretor
status in the saliva of patients with
oral pre-cancerous lesions. J Oral
Rehabil 1999; 26: 177–82.15 Javed F, Chotai M, Mehmood A,
Almas K. Oral mucosal disorders
associated with habitual gutka usage:
a review. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2010; 109:
857–64.16 Jeng JH, Chang MC, Hahn LJ. Role
of areca nut in betel quid associated
chemical carcinogenesis: current
awareness and future perspectives.
Oral Oncol 2001; 37: 477–92.17 Kinane DF, Blackwell CC, Brettle RP,
Weir DM, Winstanley FP, Elton RA.
ABO blood group secretor state and
susceptibility to recurrent urinary
tract infection in women. Br Med J
1982; 285: 423–4.18 Clark CA, Price-Evans DA, MacCon-
nel DA, Sheppard PM. Secretion of
blood group antigen and peptic ulcer.
Br Med J 1959; 1: 603–7.
19 Lamey PJ, Darwazeh AMG, Muirhead
J, Rennie JS, Samaranayake LP, Mac-
Farlane TW. Chronic hyperplastic
candidosis and secretory status. J Oral
Pathol Med 1991; 20: 67–70.20 Pourazar A, Joshi SR, Sathe MS,
Advani SH, Bhatia HM. Antigens in
leukoplakia. Indian J Med Res 1986;
89: 83–8.21 Dabelsteen E, Vedtotte P, Hakomori
S, Young WW Jr. Accumulation of
blood group antigen precursor in oral
premalignant lesions. Cancer Res
1983; 43: 1451–4.22 Dabelsteen E, Clausen H, Mandel U.
Aberrant glycosylation in oral malig-
nant and premalignant lesions. J Oral
Pathol Med 1991; 20: 361–8.23 Cerovi�c R, Jureti�c M, Balen S, Belusi�c
M, Caser L, Rogi�c M. Examining the
presence of ABO(H) antigens of
blood types in the saliva of patients
with oral cancer. Coll Antropol 2008;
32: 509–12.24 Ariyawardana GA, Panagoda J, Fer-
nando HN, Ellepola AN, Tilakaratne
WM, Samaranayake LP. Oral submu-
cous fibrosis and oral yeast carriage –a case control study in Sri Lankan
patients. Mycoses 2005; 50: 116–20.25 Koneru A, Hallikeri K, Shubhda C,
Naikmasur VG, Kulkarni RD. Com-
parative study of Candida in oral sub-
mucous fibrosis and healthy in
individuals. Rev Odonto Cienc 2011;
26: 71–6.26 Fiueld EA, Field JK, Martin MV. Does
Candida have a role in oral epithelial
neoplasia? J Med Vet Mycol 1989; 27:
277–94.27 Orlow I, Lacombe L, Pellicer I. Phe-
notypic and genotypic characteriza-
tion of the histoblood group ABO
ª 2014 Wiley Publishing Asia Pty Ltd 5
K. Hallikeri et al. Salivary secretory status
(H) in primary bladder tumors. Int J
Cancer 1998; 75: 819–24.28 Periyavan S, Sangeetha SK, Marimu-
thu P, Manjunath BK, Seema DM.
Distribution of ABO and Rhesus-D
blood groups in and around Banga-
lore. Asian J Transfus Sci 2010; 4:
41–2.29 Das PK, Nair SC, Harris VK et al.
Distribution of ABO and Rh-D blood
groups among blood donors in a ter-
tiary care centre in South India. Trop
Doct 2001; 31: 47–8.30 Reddy KS, Sudha G. ABO and Rh(D)
blood groups among the Desuri Red-
dis of Chittur District, Andhra Pra-
desh. Anthrapol 2009; 11: 237–8.31 Biondi C, Campi C, Escovich L, Gar-
cia B, Racca A, Cotorruelo C. Loss of
A, B, and H antigens in oral cancer.
Immunologica 2008; 27: 127–31.32 Bryne M, Thrane PS, Dabelsteen E.
Loss of expression of blood group
antigen H is associated with cellular
invasion and spread of oral squamous
cell carcinoma. Cancer 1991; 67: 613–8.
33 Lamey PJ, Douglas PS, Napier SS.
Secretor status and oral cancer. Br J
Oral Maxillofac Surg 1994; 32: 214–7.
34 Raghavan VM, Bailoor DN, Jhansirani
P. Incidence of ABO blood groups
in oral cancer in South Kanara dis-
trict. J Indian Dent Assoc 1986; 58:
305–8.35 Toto PD, Nadimi H. Co-expression
of cytokeratins, involucrin and blood
group antigens in oral squamous cell
carcinoma. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 1990; 70:
75–80.
6 ª 2014 Wiley Publishing Asia Pty Ltd
Salivary secretory status K. Hallikeri et al.