Non-keratinized Mucosa Research Articles

A New Tunnel Technique With Acellular Dermal Matrix for Soft Tissue Preparation Prior to Symphyseal Block Graft—A Description of Technique and Case Report

The aim of this report was to describe a newly designed tunnel technique (A New Tunnel Technique) using acellular dermal matrix (ADM) allograft for soft tissue augmentation prior to mono-cortical block graft. Two cases with vertical and horizontal ridge deficiency in the mandibular anterior area were indicated for mono-cortical block grafting before implant placement. Soft tissue evaluation and measurements showed thin tissue covering the defect area composed mainly of nonkeratinized alveolar mucosa measuring 1 to 2 mm in most of the sites. Soft tissue augmentation was done first using a new tunnel technique with ADM allograft. After 2 months of healing, mono-cortical block graft was harvested from the mandibular symphysis area and fixed to the recipient site. Soft tissue measurements were made before soft tissue graft and immediately before block graft. Healing was evaluated at 2, 4, 12, and 24 weeks post-block grafting surgery to evaluate healing. In both cases, there was generalized 1- to 2-mm increase in soft tissue thickness covering the defect areas following allograft. Both cases had healed uneventfully with no soft tissue complications following block grafting procedure to the time of implant placement. The new tunnel technique for soft tissue augmentation using acellular dermal matrix allograft seems to be a valid approach in soft tissue preparation prior to mono-cortical block grafting. Further research is needed to evaluate if this procedure will help to prevent soft tissue complications associated with block grafting.

A new therapeutic candidate for oral aphthous ulcer: Allicin

Recurrent aphthous ulcer (RAU) is the most common ulcer of oral non-keratinized mucosa, but the treatment is always limited at present. Considering the multifactorial etiology of RAU, a novel therapeutic agent with multi-bioactivties should be presented. Garlic has been recognized as a favorable natural medicine against a large number of pathologic conditions. The major component of garlic is allicin, which could effectively decrease inflammatory factors secretion, reduce the migration of neutrophils, inhibit bacterium and virus, antagonize oxidation and regulate immunity. By these bioactivities of anti-inflammation, anti-microbial activity, anti-oxidation and immunomodulation, the allicin may be an effective therapeutic candidate to control the pain, promote ulcer healing and prevent the recurrence of RAU.

Surgical Technique for Use of Autologous Buccal Mucosa Vaginoplasty in Children: Video

PURPOSE Vaginal replacement surgeries often require donor materials such as skin grafts, myocutaneous flaps, or bowel, each with significant disadvantages. We describe our technique using autologous buccal mucosa grafting for partial or complete neovagina creation. MATERIAL AND METHODS Our indications for buccal mucosa vaginoplasty have included primary repair of congenital defects such as vaginal agenesis (Mayer-Rokitansky syndrome), cloacal abnormalities, and intersex disorders as well as secondary repair of postsurgical vaginal defects like vaginal stenosis after vaginoplasty or pelvic extenteration. This video demonstrates our surgical technique in a Mayer-Rokitansky syndrome patient. RESULTS A transverse incision is made over the mucosal prominence at the level of the expected location of the hymen. Blunt dissection and electrocautery are used to dissect between the urethra and anorectum to depth 8 cm and width 3 fingerbreadths. Bilateral buccal mucosa is harvested, prepared on the bench and sewn end to end. The graft mid-portion is secured with interrupted 4-0 chromic to the apex of the previously dissected vaginal vault. The meshed graft is then stretched and tacked into position with interrupted 4-0 chromic sutures to achieve 360 degree coverage of the entire neovaginal area. A spongy vaginal mold is left in-situ for 5-7 days. CONCLUSIONS Buccal mucosa generates a moist, hairless, nonkeratinized neovaginal mucosa with excellent color and texture matching the genital/vaginal skin. It leaves no visible surgical scars, avoids abdominal bowel surgery and has no excess mucous production. It is an ideal replacement material for primary or secondary vaginoplasty with excellent early results.

Surgical Technique for Use of Autologous Buccal Mucosa Vaginoplasty in Children: Video

PURPOSE Vaginal replacement surgeries often require donor materials such as skin grafts, myocutaneous flaps, or bowel, each with significant disadvantages. We describe our technique using autologous buccal mucosa grafting for partial or complete neovagina creation. MATERIAL AND METHODS Our indications for buccal mucosa vaginoplasty have included primary repair of congenital defects such as vaginal agenesis (Mayer-Rokitansky syndrome), cloacal abnormalities, and intersex disorders as well as secondary repair of postsurgical vaginal defects like vaginal stenosis after vaginoplasty or pelvic extenteration. This video demonstrates our surgical technique in a Mayer-Rokitansky syndrome patient. RESULTS A transverse incision is made over the mucosal prominence at the level of the expected location of the hymen. Blunt dissection and electrocautery are used to dissect between the urethra and anorectum to depth 8 cm and width 3 fingerbreadths. Bilateral buccal mucosa is harvested, prepared on the bench and sewn end to end. The graft mid-portion is secured with interrupted 4-0 chromic to the apex of the previously dissected vaginal vault. The meshed graft is then stretched and tacked into position with interrupted 4-0 chromic sutures to achieve 360 degree coverage of the entire neovaginal area. A spongy vaginal mold is left in-situ for 5-7 days. CONCLUSIONS Buccal mucosa generates a moist, hairless, nonkeratinized neovaginal mucosa with excellent color and texture matching the genital/vaginal skin. It leaves no visible surgical scars, avoids abdominal bowel surgery and has no excess mucous production. It is an ideal replacement material for primary or secondary vaginoplasty with excellent early results.

Engineered Keratinized Oral Mucosa Decreased C. albicans Transition Through the Production of Keratins 10, 14, 16, and 19 by Oral Epithelial Cells

The aim of this study was to evaluate the link between Candida albicans growth and dimorphism and the pro- duction of keratins by oral epithelial cells. Various culture models (monolayer and non-keratinized and keratinized engi- neered human oral mucosa) were produced and used for this purpose. Cell morphology, tissue structure, and the transition of C. albicans were assessed following cell and tissue infections. Keratin production by epithelial cells exposed to C. albi- cans was evaluated by Western blotting. Following contact with C. albicans, epithelial cells in the monolayer cultures showed differentiating phenotypes. Compared to the keratinized tissue, the non-keratinized mucosa displayed visible dis- organization. The transition of C. albicans from blastospore to hyphal form was significantly lower in the keratinized oral mucosa model. This was correlated with the high levels of differentiating (K10) and proliferating (K14, K16, and K19) keratins in the keratinized tissue, suggesting that tissue stratification contributes to controlling C. albicans pathogenicity via keratin production. Thus, the transition of C. albicans from blastospore to hyphal form may be linked to keratin pro- duction. This may ultimately have implications in the control of oral candidiasis as well as in denture design to prevent denture stomatitis.

A Comparative Study of the Surfaces of Normal Oral Epithelia and Inflammatory Hyperplasias by Scanning Electron Microscopy

The oral epithelia may show epithelial changes induced by the inflammation of the underlying lamina propria. Light microscopically, the epithelial changes are similar to epithelial dysplasia seen in a premalignant lesion. A scanning electron microscope permits a resolution higher than that of a light microscope. Therefore, it may elucidate the changes observed light microscopically. The purpose of this study was to examine the surface changes of the epithelia of parulides (gum boils) compared with those of normal oral epithelia to see if there were any surface changes due to the underlying inflammatory processes. A total of 3 specimens (1 buccal mucosa, 1 gingiva, and 1 hard palate) taken from 3 patients, one specimen from each patient, were used as controls. A total of 2 parulides from 2 patients, 1 specimen from each patient, were used as experimentals. Each specimen was cut in two. One half was prepared for light microscopy and the other half was prepared for scanning electron microscopy. Light microscopically, it was confirmed that the buccal mucosa was nonkeratinized, the gingiva was parakeratinized, and the hard palate was orthokeratinized. The epithelium of the parulis was nonkeratinized to parakeratinized with increased intercellular spaces and distinct epithelial changes similar to epithelial dysplasia. By scanning electron microscopy, the nonkeratinized mucosa (buccal mucosa) showed that most of the ridges ran parallel to each other and the parakeratinized mucosa (gingiva) and the orthokeratinized mucosa (hard palate) exhibited ridges surrounding uniform pits. The surface of the parulis of the first patient showed relatively smooth areas with residual pits, reminiscent of that of keratinized mucosa, and the surface of the parulis of the second patient showed relatively smooth areas with residual parallel ridges, reminiscent of that of nonkeratinized mucosa. Light microscopically, the oral epithelia overlying the intensely inflamed lamina propria showed distinct epithelial changes similar to epithelial dysplasia seen in a precancerous lesion but appeared normal except for markedly decreased numbers of microridges by scanning electron microscopy.

Melanocyte transfer via epidermal grafts for vitiligo of labial mucosa.

Physiologic pigmentation of labial mucosa is seen regularly in dark-skinned races. Vitiligo of nonkeratinized labial mucosa is often visible while talking and is a cosmetic problem. Medical therapies are not effective, and surgical therapies have not been tried for this site. To study the efficacy of melanocyte transfer through contact of intact epidermal grafts with abraded labial mucosa. Seven patients (five females and two males, age range from 17 to 29) with vitiligo of labial mucosa with or without involvement of vermilion were included in the study. Affected labial mucosa was dermabraded, and suction blister grafts were transferred over these areas. After 7 days, both dressing and grafts were removed, and photochemotherapy was started. Excellent color match and repigmentation were seen in all patients after 4 to 6 weeks. The proposed modification in a well-established procedure of epidermal grafting is safe and effective. It is less time consuming and simpler than melanocyte culture, although the results are equivalent. There is no actual trans-plantation of keratinized skin, as it was removed.

Differential expression of cornified cell envelope precursors in normal skin, intraorally transplanted skin and normal oral mucosa.

Skin flaps have routinely been used as substitutes for oral mucosa after extensive resection of oral tissues. However, it remains unknown how the transplanted skin flaps perform as a host defence in the new environment of the oral cavity. To evaluate the expression of cornified cell envelope (CCE) precursors in pretransplanted (normal) skin, intraorally transplanted skin and normal oral mucosa, because CCEs are highly responsible for a protective barrier in each type of epithelium. We used immunohistochemistry and immunoelectron microscopy to examine the expression of CCE precursors, small proline-rich protein (SPR) 2 and 3 and loricrin, in biopsy specimens of normal skin, transplanted skin and normal oral mucosa, including buccal and lingual (non-keratinized) mucosae, and palatal (keratinized) mucosa. Transplanted skin flaps were classified into two groups. About two-thirds of the transplanted skin flaps displayed a reddish appearance and were devoid of the stratum corneum (SC) together with a psoriasiform inflammatory tissue reaction. Others showed a native appearance, retaining the SC. While SPR2 expression was limited to the stratum granulosum (SG) in both normal and transplanted skin retaining the SC, it extended to the stratum spinosum (SS) of the transplanted skin lacking the SC and that of the normal oral mucosa. Although SPR3 expression was not found in normal skin or in the transplanted skin retaining the SC, it was strongly expressed in the SS of the transplanted skin lacking the SC and the non-keratinized oral mucosa, and in the SS and SG of the keratinized oral mucosa. Loricrin, which was expressed in the SG of normal skin, the transplanted skin retaining the SC and the keratinized oral mucosa, was not detected in the transplanted skin lacking the SC or in the non-keratinized oral mucosa. Immunoelectron microscopy confirmed the ultrastructural localization of SPR3 directly under the cytoplasmic membrane of keratinocytes of the transplanted skin lacking the SC and that of the oral mucosa. The altered expression of SPR2, SPR3 and loricrin reflects the possible adaptation of epidermal keratinocytes in the new environment of the oral cavity.

Etiology and Management of Recurrent Aphthous Stomatitis.

Recurrent aphthous stomatitis (RAS) is an ulcerative condition that affects the oral mucosa without evidence of an underlying medical disorder. RAS is characterized by the appearance of round, shallow ulcerations surrounded by inflammation that chiefly involves the nonkeratinized mucosa. The etiology of RAS is unknown, but has a strong hereditary component and appears to be related to an immune reaction against the oral mucosa. RAS must be distinguished from other diseases that cause recurring oral ulcers such as Behçet's syndrome, systemic lupus erythematosus, and Crohn's disease. This paper reviews the current theories regarding the etiology of RAS, the clinical evaluation of patients with recurring aphthous ulcers, and describes current treatment options for this condition.

Evaluation of Inductive effect of palatal connective tissue on alveolar mucosa after subepithelial connective tissue graft: A clinical & histological study

The present clinical & histologic trial was designed to investigate the inductive effect of palatal connective tissue on the alveolar mucosa. 11 subjects 19-49 years of age showing good performance in oral hygiene were selected from Shiraz dental school patients. The test tooth (incisor, canine or premolar) had keratinized gingiva equal of less than 2 mm. This tooth together with the adjacent mesial and distal teeth should be free of gingivitis or periodontitis. The base line clinical measurements were done on the test tooth and mesial and distal adjacent teeth. Surgical phase included a mucosal flap at recipient site (with minimal thickness) at the mucogingival line of the test tooth extending somewhat to buccal of adjacent mesial & distal teeth. The remaining tissue on the bone of the area was removed and the bone was exposed. At the donor site (palate), a mucosal flap was reflected and a piece of connective tissue with thickness of 1-2 mm was removed and sutured at the recipient site & then it was covered by overlying flap. The sutures were removed after 7 days. Maintenance phase was performed by regular follow up visits up to 6 months. Six months postoperatively the base line measurements were repeated. Biopsy specimens were obtained from the grafted area and the adjacent intact alveolar mucosa. The specimens were fixed and sent for histologic examination. Data analysis showed that the keratinized and attached gingiva of test teeth and the adjacent mesial & distal teeth increased significantly clinically the added keratinized gingiva was tightly bound to underlying tissues. The probing depth & gingival recession of test teeth did not increased significantly. The light microscopic histoligic examination showed keratinization in 80% of cases. In 30% of cases dense well organized collagen bundles was seen in lamina propria. This study proved that palatal connective tissue graft can induce nonkeratinized alveolar mucosa into masticatory mucosa.

Clinico-Histopathological features and investigations of oral aphthous stomatitis including Behcet’s Disease

The three clinical subtypes of oral recurrent aphthous stomatitis (RAS) i.e. minor, major and herpetiform share certain common features - namely the patients affected are otherwise well, their ulcers have a tendency to recur, are generally associated with varyng degrees of pain and preferentially occur in nonkeratinized mucosa. These subsets of RAS differ from one another by the size and number of ulcers at each bout and wether or not permanent scarring occurs upon healing. Histopathologically RAS presents as a non specific ulcer characterized by a fibrinopurulent membrane covering an area of epithelial loss and deep to it granulation tissue showing a chronic inflammatory response and attempts at organization. Immunofluorescence of lesional tissue is rarely of diagnostic benefit. Haematological investigation may reveal an underlying haematinic deficiency. In Behcet's disease, RAS-like ulceration is seen in patients with multisystem disease involving other mucocutaneous surfaces, eyes (uveitis), musculoskeletal, neurological, haemotological and gastrointestinal systems. Thorough systematic work-up is necessary for these patients.

The clinical characteristics of intraoral herpes simplex virus infection in 52 immunocompetent patients

Objective. Intraoral herpes simplex virus infection is commonly mistaken for recurrent aphthous stomatitis. The purpose of this study was to describe the clinical features of intraoral herpes simplex virus infection. Study design. Fifty-two immunocompetent patients with culture-positive intraoral herpes simplex virus infection were studied. Results. The median age of the patients was 42 years. One third of the patients exhibited single ulcers; the remaining patients displayed multiple lesions. In 47 of 52 cases, the ulcers occurred on keratinized surfaces of the oral cavity; however, 5 patients had persistent ulcerations on nonkeratinized mucosa, a typical feature of herpetic ulcers in immunosuppressed patients. Of 27 patients with histories of recurrences, 22 were previously incorrectly diagnosed with recurrent aphthous stomatitis. Conclusions. Herpes simplex virus infection of the oral cavity can usually be differentiated from other causes of recurrent oral ulcerations on the basis of its clinical appearance and distribution. The recognition of atypical features may prevent unnecessary and costly treatments for unrelated though clinically similar-appearing disorders.

In vivo OCT imaging of hard and soft tissue of the oral cavity

We use optical coherence tomography (OCT) to perform a comprehensive program of in vivo and in vitro structural imaging of hard and soft tissues within the oral cavity. We have imaged the different types of healthy oral mucosa as well as normal and abnormal tooth structure. OCT is able to differentiate between the various types of keratinized and non-keratinized mucosa with high resolution. OCT is also able to provide detailed structural information on clinical abnormalities (caries and non-caries lesions) in teeth and provide guidance in dental restorative procedures. Our investigations demonstrate the utility of OCT as a diagnostic imaging modality in clinical and research dentistry.

Determination of serin, metallo- and cystein elastase in aorta at experimental arteriosclerosis

Aberrant keratinization is common in oral lichen planus (OLP) on buccal mucosa. Because elastin is crucial for maintaining the nonkeratinized phenotype of oral mucosa, we examined whether inflammatory elastases and the accompanying elastolysis were related to this feature.Protein and mRNA levels of keratinization-associated keratins (K1/10), nonkeratinization-associated keratins (K4/13), elastin, neutrophil elastase, and macrophage metalloelastase (MMP-12) were compared between normal alveolar mucosa and reticular OLP from buccal mucosa. Normal alveolar mucosae were cultured ex vivo on an organ culture system with and without elastase treatment. After 14 days, the mucosae were examined for 4 keratin expressions.The expressions of K1/10 and elastases increased, whereas those of K4/13 and elastin decreased in OLP. The nonkeratinized mucosa in the organ culture began to express K1/10 when elastase degraded the inherent elastin.Our study demonstrated that elastolysis in reticular OLP may be related to its aberrant keratinization.

Differential expression of integrins and laminin-5 in normal oral epithelia.

beta 1 and beta 4 integrins are receptors on epithelial cells mediating cell-extracellular matrix adhesion. Furthermore, alpha 2 beta 1 and alpha 3 beta 1 contribute to cell-cell adhesion. Laminin-5 in epithelial basement membranes (BMs) is a ligand for alpha 6 beta 4 and alpha 3 beta 1. Expression of different integrins and laminin-5 was studied in oral epithelium to characterize regional variations in these adhesion molecules. Monoclonal antibodies directed against alpha 2-alpha 6 beta 1/alpha 6 beta 4 and laminin-5 were examined in cryopreserved biopsies of normal mucosa by immunohistochemistry. Laminin-5 was expressed as a line along the BMs. The junctional epithelium showed a unique phenotype: Laminin-5 was detected in the internal BM at the tooth surface and in the external BM, where excessive laminin-5 was seen in the stroma. alpha 6 beta 4 was expressed in all cells of the junctional epithelium. Integrins alpha 4 beta 1 and alpha 5 beta 1 were not detected in the epithelia, whereas alpha 2 beta 1 and alpha 3 beta 1 showed differential expression. Epithelia with well-developed rete pegs and connective tissue papillae showed polarized alpha 3 beta 1 expression along the BM in the rete pegs, in contrast to negative expression at the tips of the connective tissue papillae. A variation in the suprabasal distribution of alpha 2 beta 1 and alpha 3 beta 1 was observed between epithelia from different regions. alpha 2 beta 1 and alpha 3 beta 1 were detected in basal/parabasal cells in keratinized epithelia, whereas there was increased suprabasal expression in nonkeratinized mucosa. These results indicate inhomogeneity in the basal cell population of oral squamous epithelia and differential expression of integrins, which may reflect differences in the underlying stroma. Laminin-5 deposits in the stroma underneath the junctional epithelium may indicate subclinical gingival inflammation.

Sutton's disease

Major aphthous stomatitis, also known as Sutton’s disease or periadenitis mucosa necrotica recurrens, is an extremely rare and severe form of the more common recurrent aphthous stomatitis (RAS). RAS is a disorder characterized by recurring ulceration of the nonkeratinized mucosa of the oral cavity.’ Aside from dental caries and periodontal disease, oral aphthae are the most common disorder of the oral cavity.2 RAS is thought to affect at least 20% of the population in North America, though several studies report estimates as high as 50%.~ Sutton’s disease is a rare variant of RAS characterized by recurrent, necrotizing ulcers, which persist for months and ultimately heal with a fibrous scar. Multiple etiologies have been postulated, though the cause of this debilitating disease is unknown.1-8 This report describes the case of a 28-year-old man with Sutton’s disease, who, following treatment with multiple medications, responded well to treatment with the immunosupressant agent cyclophasphamide in combination with prednisone.

Association between expression of stratum corneum chymotryptic enzyme and pathological keratinization in human oral mucosa.

Stratum corneum chymotryptic enzyme (SCCE) may function in the degradation of intercellular cohesive structures in the stratum corneum preceding desquamation. Previous results have suggested that SCCE may be specifically expressed in squamous epithelia undergoing terminal differentiation and keratinization. The aim of the present work was to further elucidate the association between SCCE expression and terminal differentiation in squamous epithelia. Using immunohistochemical methods, we have examined the expression of SCCE in two diseases of human oral mucosa, which produce a pathological keratinization of the epithelium at sites which are normally non-keratinized. Affinity-purified polyclonal rabbit antibodies raised against recombinant SCCE and monoclonal antibodies against the differentiation-specific keratins nos. 10 and 13 were used on formaldehyde-fixed and paraffin-embedded biopsies. Whereas there was essentially no expression of SCCE in normal, non-keratinized buccal mucosa, there was a strong expression in suprabasal cells in orthokeratotic and parakeratotic areas of the lesions of oral lichen planus (an inflammatory disease) and benign oral keratosis (a non-inflammatory disease). There was a close association between the expression of SCCE and keratin no. 10, i.e. a keratin which is specifically expressed in cornifying squamous epithelia. The results suggest that SCCE expression may be a true marker of terminal differentiation in squamous epithelia and give further evidence for a role of SCCE in the formation and/or turnover of the stratum corneum.

Increased elafin expression in cystic, dysplastic and neoplastic oral tissues.

Expression of human leukocyte elastase inhibitor, elafin, otherwise known as skin-derived antileukoproteinase inhibitor (SKALP), was investigated in normal and abnormal oral tissues using a specific anti-SKALP rabbit antiserum. Weak staining was observed in keratinizing epithelia of normal oral mucosa but not in non-keratinizing mucosa. Increased expression was also observed in the suprabasal layers of dysplastic oral epithelia and in well-differentiated squamous cell carcinoma, but not in basal cell carcinoma. A uniform strong expression was observed in all supra-basal layers of odontogenic keratocyst epithelia, except in regions where inflammatory infiltrate was adjacent to keratocyst epithelia. In contrast, elafin expression in a small number of dentigerous cysts and ameloblastomas was more patchy. The increased levels of elafin in keratocyst epithelia and dysplastic tissue may be a cellular homoeostatic response to generate a protective barrier preventing proteolytic degradation of underlying elastic tissue.

Gene expression of markers associated with proliferation and differentiation in human keratinocytes cultured from epidermis and from buccal mucosa

Normal keratinocytes from epidermis and from buccal mucosa underwent dissimilar stages of differentiation in the same culture medium and responded differently to changes in the composition of the medium. Manifestations of these variations were examined in terms of the expression at the mRNA level (as measured by reverse transcriptase-polymerase chain reaction) of three regulatory genes (cdc2, c- myc, and p53) and five genes that encode structural proteins (keratins K5, K10 and K13, involucrin, and filaggrin), in three growth-medium formulations. The culture conditions enhanced or retarded maturation; the observed alterations in gene expression correlated with these changes. Except for the proliferation genes, the non-keratinizing buccal mucosa generally responded more weakly than the orthokeratotic epidermis to culture-medium supplementation favouring differentiation. Gene expression in cultured keratinocytes reflected their ability to differentiate in vivo; genes were expressed even when the corresponding protein was not seen in vitro. Although keratin K10 is not prevalent in the buccal mucosa nor keratin K13 in the epidermis, the genes for both were found to be expressed in both tissues.

Co-expression of ras p21 and epidermal growth factor receptor during various stages of tumour progression in oral mucosa.

Ras p21 and epidermal growth factor receptor (EGFR) have commonly been implicated in a variety of malignancies. The present study immunohistochemically analysed the relationship between the expression of ras p21 and EGFR in normal, premalignant and malignant lesions of the oral mucosa. Except for normal mucosa, all other lesions showed a more or less similar expression pattern of both ras p21 and EGFR. It was also observed that the expression of both proteins was mostly confined to the basal or basaloid cells of the leucoplakia and carcinoma lesions, respectively. Normal keratinizing type mucosa showed expression of ras p21 and EGFR in the basal and lower spinal cells. However, in non-keratinizing mucosa the expression of ras p21 was totally negative while EGFR was restricted to the basal cells. Statistical analysis revealed a good correlation between the expression of ras p21 and EGFR with the various histological stages of tumour progression. The presence of these proteins in immature dividing cells of premalignant and malignant lesions thus emphasizes their relationship with cell proliferation.