Solid Multicystic Ameloblastoma Research Articles

A Comparative Evaluation of Collagen in Ameloblastoma and Oral Squamous Cell Carcinoma using Picrosirius Red Staining with Polarizing Microscopy and CD44v6 Immunoreactivity.

Solid multicystic ameloblastoma (SMA) is a locally aggressive, benign odontogenic tumor of odontogenic origin with greater rate of recurrence. Epithelial-mesenchymal interaction plays an important role in tooth morphogenesis that shows complete differentiation of epithelial and ectomesenchymal components to the level of tooth formation. Tumor stroma in ameloblastoma is normal mature collagen that prevents differentiation to the level of tooth formation. Current study evaluates the role of stromal elements in aggressive behavior of SMA using picrosirius red staining with polarizing microscopy and CD44v6 immunohistochemistry (IHC). To compare nature of collagen using picrosirius red staining under polarized microscope and IHC expression of CD44v6 marker in SMA and oral squamous cell carcinoma (OSCC). Thirty blocks were retrieved from departmental archives and subjected to picrosirius red staining and CD44v6 IHC staining. Slides stained with picrosirius red were observed under polarized microscope to report the birefringence pattern. IHC slides were annotated for intensity of staining of tumor cells. In contrast to OSCC's 40% red, 40% yellowish-red, and 20% greenish-yellow birefringence, SMA displayed 87% red, 13% yellowish-red, and 0% greenish-yellow. Compared to OSCC, which had tumor cells stained 9% strongly, 64% moderately, 27% mildly, and 0% negatively, SMA revealed 0% strong, 10% moderate, 60% weak, and 30% negative staining. As opposed to OSCC, which exhibited a greater quantity of greenish-yellow birefringence of immature collagen, SMA showed predominantly red birefringence, which is suggestive of mature collagen with a lack of metastasis. Comparing SMA to OSCC, the lack of significant CD44v6 positivity suggests that there has not been perineural invasion or regional metastases in SMA.

A network meta-analysis assessing the effectiveness of various radical and conservative surgical approaches regarding recurrence in treating solid/multicystic ameloblastomas

Multiple treatment approaches have been undertaken to reduce the incidence of recurrence in solid/multicystic ameloblastoma (SMA), both conservative and radical. A network meta-analysis (NMA) was conducted to assess and compare the effectiveness of these various treatment approaches concurrently. This study was reported based on the Preferred Reporting Items for Systematic Reviews for Network Meta-Analysis (PRISMA-NMA) statement. PubMed (MEDLINE), ScienceDirect, Scopus, and Web of Science were searched until August 10, 2021. The NMA was conducted using the STATA program. Of 1153 records identified in the search, seven observational studies with 180 patients were included. Six different treatment approaches were identified. Segmental resection ranked highest for reducing the recurrence rate with the highest SUCRA score (77.7), followed by curettage with cryotherapy (66.9) and marginal resection (49.3). Network inconsistencies and publication bias appeared to be absent. According to the Confidence in Network Meta-Analysis (CINeMa) method, the evidence's certainty was low for all comparisons due to imprecision and within-study bias. In conclusion, this study is the first NMA in the field of ameloblastoma. Segmental resection seemed to be the most effective treatment approach for minimizing recurrence in SMA patients. Nevertheless, weak certainty of evidence makes that the results must be regarded with caution.

Segmental resection vs. partial resection on treating solid multicystic ameloblastomas of the jaws - recurrence rates: A systematic review and meta-analysis.

The aim of the present study was to compare the recurrence rates of solid multicystic ameloblastomas after segmental resection or marginal resection. PubMed, ScienceDirect, Web of Science, Scopus, Embase were searched for studies published up to July 2022. The gray literature was also searched. Meta-analysis was performed using OpenMeta Software, p< 0.05 considered significant. Among the search, 8 studies met all eligibility criteria. The group that underwent marginal resection was 1.1 times more likely to present recurrence of the lesion compared to the group that underwent segmental resection. There was no statistically significant difference between the two groups (segmental resection and marginal resection) in all eight studies regarding reducing ND (95% Confidence interval, 0.339 - 3.705; heterogeneity: Q value= 3.105; I2= 0%). The results showed that there was no statistically significant difference between segmental and marginal resection for the treatment of solid multicystic ameloblastomas; however, prospective studies with more rigorous methodological procedures are needed to better compare the surgical techniques. Key words:Ameloblastoma, solid multicystic ameloblastoma, treatment, recurrence.

Histopathologic Feature of Hyalinization Predicts Recurrence of Conventional/Solid Multicystic Ameloblastomas.

The histologic properties of tumors seem to affect their biological behavior, and the same holds good for solid multicystic ameloblastoma (SMA), a benign, locally destructive lesion. Hyalinization is one such histological factor that has been demonstrated to correlate with the biological behavior of neoplasms. The present study aimed to analyze the correlation between the severity of hyalinization (SOH) and the recurrence potential of SMAs. The study was performed on formalin-fixed, paraffin-embedded (FFPE) diagnosed archival cases of SMA, follicular SMA (n = 35) and plexiform SMA (n = 25). The cases were evaluated for SOH and scored from 0–3, and the correlation between SOH and recurrence was analyzed for statistical significance. The clinical parameters of the lesion were analyzed for statistical correlation with recurrence. The SOH significantly correlated with the recurrence of SMA (p = 0.001). The histologic type did not influence the biological behavior of SMA. The location of SMA in the body of the mandible (p = 0.036), multilocular radiolucency (p = 0.001) and root resorption (p = 0.002) also showed strong statistical correlation with recurrence. It is evident from the present study that hyalinization strongly correlates with the biological behavior of SMA. Future studies with advanced investigations could validate the presence of hyalinization and identify the origin of the hyalinized product in SMAs.

CORRELATION OF SYNDECAN 1 EXPRESSION IN SOLID AND UNICYSTIC AMELOBLASTOMA AND ITS CELLULAR COMPONENTS

<h3>Background</h3> Syndecan-1 (SDC1) is a transmembrane heparan sulfate proteoglycan (also known as CD138), participates in odontogenesis, and is known to regulate cytoskeletal organization, growth factor signaling, cell–cell adhesion, and extracellular matrix attachment. Loss of expression of SDC1 is associated with tissue invasion, metastasis, and poor prognosis. <h3>Objective</h3> To study the syndecan expression in solid and unicystic ameloblastoma and to assess and compare the distribution of the SDC1 in various cellular components of the solid multicystic and unicystic ameloblastoma and correlate with their differentiation and biological behavior. <h3>Methods</h3> Samples in this study consisted of 50 cases: 25 cases of solid multicystic ameloblastoma and 25 cases of unicystic ameloblastoma. Formalin-fixed, paraffin-embedded tissue sections were immunohistochemically analyzed for SDC1 markers. Expression of syndecan was measured under 400 × magnification in the solid ameloblastoma in epithelium where lesional cells are composed of 4 types of cellular components: peripheral basal cells of tumor nests, central stellate reticulum-like cells, and foci of squamous and granular cells. Unicystic ameloblastoma was checked for its cystic lining. Stromal expression of SDC1 was also evaluated in fibroblast-like or spindle cells. Plasma cells served as internal controls for the study. The findings were statistically analyzed. <h3>Results</h3> Comparison of the epithelial cell scoring was higher in unicystic than in solid ameloblastomas. However, the stromal expression was greater in solid ameloblastomas, moderately increased around the follicles and to a lesser extent in the deeper connective tissues. <h3>Conclusions</h3> Syndecan proved to be a useful marker to assess and compare the biologic behavior of solid and unicystic ameloblastomas.

Modified conservative management of mandibular ameloblastoma: a 13‐year experience in a Malaysian tertiary care centre

AbstractPurposeAlthough surgical resection is routinely used to treat mandibular ameloblastoma, it associates with aesthetic and functional complications, hence a modified conservative management (MCM) comprising surgical enucleation, peripheral ostectomy and chemical cauterisation was practiced in a tertiary care centre in northern Malaysia. This study aims to access the treatment outcome and potential use of MCM.MethodsThis cross‐sectional study assessed the demographic and clinical profiles of mandibular ameloblastomas managed with MCM and their outcomes from year 2006 to 2019.ResultsA total of 13 cases of mandibular ameloblastoma were identified between 2006 and 2019 with MCM, which consisted of nine cases of solid/ multicystic ameloblastoma (SMA) (84.6%), and two cases of unicystic ameloblastoma (UA). Over mean review duration of 57 month, three recurrences (23.2%) were reported for SMA group and no recurrence was found for UA cases.ConclusionsThe relatively low recurrence rates suggest that MCM has potential to be used as an alternative treatment for mandibular ameloblastoma. Further well‐designed prospective study is recommended to understand the effectiveness of MCM, which hopefully can evolve towards a minimally invasive surgical approach in treating mandibular ameloblastoma.

Consistency of color-deconvolution for analysis of image intensity of alpha smooth muscle actin-positive myofibroblasts in solid multicystic ameloblastomas

ABSTRACT Ameloblastoma is an odontogenic tumor with a slow, locally aggressive growth pattern and multiple clinico-histologic types. The number of stromal myofibroblasts within ameloblastoma often is correlated with growth and aggressiveness. Color-deconvolution to separate different colors of immunostained tissues is a promising approach to quantifying myofibroblasts in tumors such as ameloblastoma. We investigated the reliability of the color-deconvolution method using cross-sectional design to evaluate alpha-smooth muscle actin (α-SMA)-positive myofibroblasts in solid multicystic ameloblastoma. Formalin fixed tissues of eight cases of solid multicystic ameloblastoma were immunostained for α-SMA using the horseradish peroxidase-diaminobenzidine (HRP-DAB) method. Color-deconvolution using ImageJ software was used to quantify the staining intensity of brown DAB α-SMA stained myofibroblasts. Color-deconvoluted images of brown DAB stained tissues exhibited distinct morphological features of solid multicystic ameloblastoma with α-SMA stained myofibroblasts distributed abundantly adjacent to the ameloblastoma epithelial islands. The computed image intensity of α-SMA stained myofibroblasts was quantitatively similar among the different ameloblastoma samples. A combination of color-deconvolution and α-SMA staining of myofibroblasts is a useful diagnostic tool for evaluating histologic differentiation and growth pattern of ameloblastoma.

Immunohistochemical expression of p53 and murine double minute 2 protein in odontogenic keratocyst versus variants of ameloblastoma.

Oncogenes and tumor suppressor genes play a major role in cancer formation, growth, and progression. One of the important findings in this area is that murine double minute 2 (MDM2) oncogene is a negative regulator of wild-type p53. In tumors, expressing wild-type p53, inhibition of MDM2 expression will stabilize p53 and allow it to perform its proapoptotic function, while simultaneously preventing MDM2 from exerting its p53-independent oncogenic effects. The intracellular levels of p53 are tightly regulated by MDM2, as it is a key player in autoregulatory feedback loop under nonstressed conditions. The p53-MDM2 relationship is vital not only for essential functions of the cell, but it also appears to be an integrated part of the complex cellular network which supports the importance of this affair and is a hallmark for its coexistence. This study was designed to identify immunohistochemically the expression of p53 and MDM2 gene using monoclonal antibody in 60 cases of formalin-fixed paraffin-embedded tissue blocks, of which 20 cases were of solid multicystic ameloblastoma (SMA), 20 cases were of odontogenic keratocyst (OKC), and 20 cases were of unicystic ameloblastoma (UA). Immunoexpression of p53 and MDM2 was highest in OKC followed by SMA and was minimum in UA. Further results showed positive correlation between both the molecules. The studied showed that the relationship has a significant role in cancer etiology and progression and therefore is an important topic for future research which should help in the development of new therapeutic agent against cancer.

Aggressive osteolytic lesion of mandible - A case report

Odontogenic tumors are rare entities, often derived from epithelial remnants in the gnathic bones following odontogenesis. Ameloblastoma is benign locally invasive accounting for 1% of tumors of jaws. Among the various ameloblastoma, solid multicystic ameloblastoma is believed to be locally aggressive lesion that has the tendency for recurrence. In this report, we present a large aggressive solid multicystic ameloblastoma in a 33-year-old male patient diagnosed by computed tomography and successfully managed by hemimandibulectomy with simultaneous reconstruction using fibula. We have also briefly discussed the molecular pathogenesis and new treatment aspects of ameloblastoma.

SYNCHRONOUS EXPRESSION OF E-CADHERIN AND SYNDECAN-1 IN AMELOBLASTOMA: A PRELIMINARY STUDY

Objectives This study aimed to evaluate the percentage of expression and the possibility of synchronicity between E-cadherin (Ecad) and Epithelial syndecan-1 (Syn-1E) in Unicystic ameloblastoma (UAM) and solid multicystic ameloblastoma (SMA) and the association between this synchronicity and stromal immunoexpression of Syn1 (Syn1S). Findings Immunohistochemical analysis of Ecad and Syn1 was performed for 30 (15 UAM, 15 SMA) cases of ameloblastoma, the percentage of expression was evaluated with the average value for expression, and intensity was evaluated with the Immunomebrane plug-in. (Image J, BioMediTech, Finland) The percentage expression of Ecad and Syn1E was high in UAM. (p 0.05) Conclusions We observed synchronicity in the expression of Ecad and Syn1E in both types of ameloblastomas. The adhesiveness of the tumoral cells is probably related to the regulation of expression of both proteins; thus, an increase or reduction of synchronicity is related to cell invasion and the capacity to migration to the stroma, which was reflected in the behavior of the ameloblastomas in the present cases. This assumption may be further supported by an increase in expression of Syn1S in the SMAs; therefore, it is possible that the low synchronicity between Ecad and Syn1E constitute an important factor for the aggressiveness of ameloblastomas.

Immunohistochemical Expression of Myofibroblasts Using Alpha-smooth Muscle Actin (SMA) to Assess the Aggressive Potential of Various Clinical Subtypes of Ameloblastoma.

Objective:Ameloblastoma is a rare odontogenic neoplasm with high recurrence rates if improperly treated. If left untreated (or is treated inadequately), it can cause substantial morbidity, disfigurement, and even death. Hence, there is a need to explore the stromal cells too, which might play an important role in assessing its aggressive behavior and may help to predict the recurrence of different clinical variants of ameloblastoma. Myofibroblasts (MFs) are such cells which have been studied in various lesions.Materials and Methods:This retrospective study involved archival tissues of ameloblastoma. Among a total of 40 cases, 12 cases of SMA (solid multicystic ameloblastoma), 10 cases of unicystic ameloblastoma (UA), 8 cases of desmoplastic ameloblastoma, and 10 cases of oral squamous cell carcinoma were selected as control. Immunohistochemical staining with anti-alpha-smooth muscle actin antibody was done. Interpretation of ten examined fields was counted by three observers.Results:Significant difference in the number of MFs in SMA and UA and desmoplastic ameloblastoma and UA (P < 0.05) was found. However, there was no statistically significant difference in MFs of SMA and desmoplastic ameloblastomas (P > 0.05). In addition, there was no statistically significant difference in the staining intensity between the three variants (P > 0.05).Conclusion:A significant correlation was obtained between the number of MF in all the three clinical variants, i.e., SMA, UA, and desmoplastic ameloblastoma (P = 0.02), which is the unique feature of the study.

Genetic alteration of Exon 5 of the PTEN gene in Indian patients with ameloblastoma

The PI3K/Akt/mTOR pathway is one of the signaling pathways associated with the pathogenesis of ameloblastoma. The phosphatase and tensin (PTEN) homologue controls cell migration and proliferation. It monitors the level of Akt and maintains cellular integrity. The aim of the present study was to study the genetic alteration of Exon 5 of the PTEN gene in Indian patients with ameloblastoma. Total DNA was extracted from formalin-fixed paraffin-embedded tissue samples from 20 cases with solid multicystic ameloblastoma (SMA) and from 10 cases with normal tooth germ. Exon 5 of the PTEN gene, was assessed for its role in the pathogenesis of ameloblastoma. Five of 20 cases of SMA showed genetic alteration. Of these cases 3 (15%) showed silent mutation, 1 (5%) showed change in amino acid sequence from valine to glutamic acid, and 1 (5%) showed nonsense-mediated mRNA decay. The present study showed 25% somatic mutational frequency in exonic region 5 of the PTEN gene. This may indicate its role in the pathogenesis of ameloblastoma.

Enhanced basal autophagy supports ameloblastoma-derived cell survival and reactivation

ObjectivesAmeloblastoma is an aggressive odontogenic jaw neoplasm. Its unlimited growth confers high potential for malignant transformation and recurrence. It is unclear why ameloblastoma is highly recurrent despite surgical resection with a wide margin of normal tissue. While canonical autophagy can be used to degrade and eliminate damaged cellular components, it is also a protective mechanism that provides energy and vital metabolites for cell survival. We used ameloblastoma-derived cells to test the hypothesis that autophagic processes play a role in survival and reactivation of ameloblastoma. MethodsPrimary epithelial (EP-AMCs) and mesenchymal (MS-AMCs) ameloblastoma-derived cells were established from tissue samples of solid multicystic ameloblastoma. Clonogenic capacity and basal autophagic capacity were assessed in ameloblastoma-derived cells relative to human odontoma-derived cells (HODCs) and maxilla-mesenchymal stem cells (MX-MSCs). Ability of ameloblastoma-derived cells to survive and form new ameloblastoma was assessed in mouse tumor xenografts. ResultsEP-AMCs were highly clonogenic (p < 0.0001) and demonstrated enhanced basal levels of autophagic proteins microtubule-associated protein 1-light chain 3 (LC3) (p < 0.01), p62 (Sequestosome 1, SQSTM1) (p < 0.01), and the LC3-adapter, melanoregulin (MREG) (p < 0.05) relative to controls. EP-AMCs xenografts regenerated solid ameloblastoma-like tumor with histological features of columnar ameloblast-like cells, loose stellate reticulum-like cells and regions of cystic degeneration characteristic of follicular variant of solid multicystic ameloblastoma. The xenografts also displayed stromal epithelial invaginations strongly reactive to LC3 and p62 suggestive of epithelial-mesenchymal transition and neoplastic odontogenic epithelium. ConclusionsEP-AMCs exhibit altered autophagic processes that can support survival and recurrence of post-surgical ameloblastoma cells.

Is conservative surgery a better choice for the solid/multicystic ameloblastoma than radical surgery regarding recurrence? A systematic review.

Determine if conservative surgery of primary solid/multicystic ameloblastoma (SMA) is capable of decreasing the recurrence rate as effectively as radical surgery. We searched in MEDLINE, Web of Science, Scopus and Cochrane Library for original studies reporting on the conservative or radical treatment of primary SMA and the related recurrence rate. All selected data were independently assessed. Meta-analysis was performed and the Relative Risk (RR) of recurrence with a confidence interval of 95% was the effect measure. P value for the summary effect of < 0.05 was considered statistically significant. The 2647 records retrieved were reduced to 7 studies to be qualitatively assessed and 4 studies were included in the meta-analysis. RR of 1.88 [0.59, 5.95] of the pooled values pointed that recurrence rate after the conservative surgery is neither comparable nor lower than the radical surgery (P = 0.28). Conservative surgery does not reduce the recurrence rate as efficiently as radical surgery for primary SMA. However, there is not enough evidence to support this statement.

Evaluation and Immunolocalization of BMP4 and FGF8 in Odontogenic Cyst and Tumors.

Growth factors like bone morphogenetic protein 4 (BMP4) and fibroblast growth factor 8 (FGF8) play a major role in organogenesis and specifically in odontogenesis. They are also believed to have a role in oncogenesis. Thus, any discrepancies in their standard behavior and activity would lead to serious abnormalities including odontogenic cyst and tumors. The present research work investigated the expression of BMP4 and FGF8 in odontogenic tumors (OT) and cyst as well as developing tooth germs to elucidate their roles. Dental organs of various odontogenic stages and 30 OTs including solid multicystic ameloblastomas (SMA, 10 cases), ameloblastic fibroma (AF, 10 cases), odontogenic myxoma (OM, 10 cases), and odontogenic cysts: odontogenic keratocyst (OKC, 10 cases) were evaluated in both epithelial and mesenchymal components for the expression of BMP4 and FGF8 using immunohistochemistry. The epithelial nuclear expression of BMP4 was highest in OKC (9 cases) while FGF8 was highest in SMA (10 cases). The mesenchymal nuclear expression of both BMP4 (8 cases) (p = 0.001) and FGF8 (9 cases) (p = 0.045) were significantly high in OMs among all OTs. Both growth factors were actively expressed in different stages of tooth development. The expression of BMP4 and FGF8 corelates well with the proliferative component of the pathologies, indicating a possible role in the pathogenesis and progression.

Abstract 1556: Does surgical treatment affect serum levels of vascular endothelial growth factor (VEGF) in orofacial tumors

Abstract Introduction: Angiogenesis, the generation of new vessels, is regulated by several growth factors. The most important of them is vascular endothelial growth factor (VEGF), which is closely related to tumor progression and prognosis. To my knowledge no study in sub-Saharan Africa has evaluated the level of VEGF following surgery in African patients. This study therefore aims to evaluate the pattern and clinical implication of VEGF expression in benign and malignant neoplasms and determine the effect of surgical intervention on the levels of circulating VEGF. Methods: This case-control study was carried out at the University of Benin Teaching Hospital (UBTH), Benin City, Nigeria, between October 2015 and February 2017. Cases were drawn from among histologically confirmed orofacial tumors, while controls were from consecutive, ambulatory dental patients, matched for age and sex. Calculated sample size for minimum effect was 77 for both cases and controls. Blood samples were taken from cases and controls, pre- and 1-month post-surgery, allowed to clot and serum aliquots were stored at -600 C till analyses. Post-surgery tissue was processed and stained with anti-VEGF antibody for immunohistochemical analysis. Serum VEGF was analyzed using Sandwich ELISA, and mean levels as well as median were measured. Spearman correlation was estimated, t-test measured significance (at p ≤ 0.05), and one-way ANOVA measured between group differences. Results: Following 12% attrition, 81 subjects were retained in the study (55 cases [20 malignant, 35 benign] and 26 controls). The most common malignant neoplasms were head and neck squamous cell carcinoma (35%) and polymorphous low-grade adenocarcinoma (20%), while the benign tumors were mostly unicystic ameloblastoma (42.9%) and solid multicystic ameloblastoma (31.4%). Before surgical treatment, there were significantly different serum levels of VEGF in benign (48.11 ± 25.19 pg/ml) vs. malignant cases (1065.00 ± 412.14 pg/ml), and compared with controls (45.42 ± 29.83 pg/ml), p &amp;lt;0.001. Also, the level of circulating VEGF correlated strongly and positively with tumor tissue expression in malignant cases (r = 0.674, p &amp;lt;0.001). After definitive surgical intervention, there was a significant reduction in the level of serum VEGF in both benign (45.50 ± 24.71 pg/mL) and malignant cases (51.22 ± 16.84 pg/mL), p &amp;lt;0.001. One-way ANOVA revealed no significant differences between cases and controls post-surgery. Conclusion: There were elevated levels of serum VEGF in benign and malignant orofacial neoplasia, which correlate positively with the expression of VEGF in tumor tissue. Surgery caused a significant reduction of circulating VEGF to normal levels irrespective of age, gender, previous medical history, perceived duration of the lesion and lymph node involvement. Citation Format: Aimuamwosa Obarisiagbon, Peter Egbor, Ozoemene Ndubuisi Obuekwe, Osagie Akpata, Akin Ojo, Nosayaba Osazuwa-Peters. Does surgical treatment affect serum levels of vascular endothelial growth factor (VEGF) in orofacial tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1556.

Solid Multicystic Ameloblastoma Misdiagnosed Radiographically as a Periapical Cyst: A Case Report

Ameloblastoma is a rare odontogenic neoplasm occurring in the jaw that can be observed as several different histologic and radiographic presentations. Since inadequate treatment is associated with high recurrence rate, accurate diagnosis is critical for proper management of ameloblastoma. The preferred treatment is wide local excision and reconstruction. We herein present a patient with solid multicystic ameloblastoma involving the mandible, which was initially misdiagnosed and treated as a periapical cyst, and discuss various radiographic presentations of ameloblastoma.

Expression of parathyroid hormone related protein (PTHRP) in ameloblastomas.

BackgroundPresence of parathyroid hormone related protein (PTHrP) might suggest that ameloblastomas recapitulate features of the enamel epithelium and induce bone resorption, which would facilitate their growth and local invasion. The aim of this study was to determine the expression of PTHrP in ameloblastomas.Material and MethodsAn observational research study was designed including 39 cases of histologically diagnosed ameloblastomas (39 out of 42 patients gave consent for the use of their medical records and all data required for this study). Gender, age, tumor location, histological type and subtype of the tumor were recorded and PTHrP expression was determined by indirect immunohistochemistry using monoclonal anti-human PTHrP (1D1 / Santa Cruz Biotechnology). Protein expression and intensity were evaluated under light microscope and finally data recorded and statistically analyzed. This research was approved by the Caracas West General Hospital review board.Results39 cases of ameloblastomas were evenly distributed between genders (49% male and 51% female) with a mean age of 33 ± 3.53 years, mainly affecting the posterior mandible. 20 cases (51.28%) showed positive cytoplasmic immunoreactivity to PTHrP. 8 out of 15 cases of solid/multicystic ameloblastomas and 12 out of 23 cases of unicystic ameloblastomas were PTHrP positive. Intense expression of PTHrP was observed in 4 unicystic ameloblastomas (all luminal subtype) and in 5 cases of conventional ameloblastomas.ConclusionsIn the present study PTHrP expression in solid multicystic and unicystic ameloblastoma suggests its possible function in the biological behavior of the tumor. More studies are needed in order to determine the possible role of this protein related to bone invasion processes. Key words:Parathyroid hormone related protein, PTHrP, ameloblastoma, bone.

Stem Cell Markers SOX-2 and OCT-4 Enable to Resolve the Diagnostic Dilemma between Ameloblastic Carcinoma and Aggressive Solid Multicystic Ameloblastoma.

Background:Ameloblastic carcinoma (ACA) is a malignant neoplasm with overlapping histopathological features of benign aggressive solid multicystic ameloblastoma (SMA). This often leads to misdiagnosis with direct implication on the management protocol. The need of the hour is to adopt reliable tissue biomarkers to differentiate these lesions accurately that will help to implement an appropriate treatment modality. Few studies to differentiate ACA and SMA in literature with a limitation of a single marker and lack of availability of cases have prompted us to undertake this study. Thereby, this study is aimed at resolving the diagnostic dilemma in differentiating ACA and aggressive SMA using SOX-2, OCT-4 and CD44.Materials and Methods:Tissue samples involved 40 archival cases of histopathologically confirmed cases of ACA (n = 20) and SMA (n = 20). The sections were subjected to immunohistochemical staining using antibodies to SOX-2, OCT-4 and CD44. Nuclear staining for SOX-2 and OCT-4 and membranous reactivity for CD44 was considered positive.Results:The expression of SOX-2 and OCT-4 in ACA was statistically significant when compared to SMA (P < 0.001). CD44 showed an insignificant statistical value of <0.077 in differentiating ACA and SMA. SOX-2 and OCT-4 expression in ACA showed a significant correlation coefficient of 0.616 at P < 0.004.Conclusions:SOX-2 and OCT-4 could serve as independent novel markers in resolving the diagnostic dilemma between ACA and aggressive SMA.

Cancer stem cell markers, SOX 2 and OCT 4 in ameloblastoma and keratocystic odontogenic tumor: An immunohistochemical study

Background: SOX 2 and OCT 4 are cancer stem cell (CSC) markers required for the maintenance of pluripotency and self-renewal of stem cells. They have been found to play a role in tumorigenesis. This study was conducted to detect and compare the expression of CSC markers OCT 4 and SOX 2 in ameloblastoma and keratocystic odontogenic tumor (KCOT) and to evaluate which marker better stains the stem cell population in the above-mentioned entities. Materials and Methods: Paraffin sections of 15 KCOT's and 15 solid multicystic ameloblastomas were obtained from the archives. Immunohistochemical staining for OCT 4 and SOX 2 was performed using monoclonal rabbit antibodies (PathnSitu Biotechnologies Pvt. Ltd). Immunopositivity was determined on the basis of dark brown staining of nucleus and a total of 1000 cells were counted in five representative areas at a magnification of ×400. Results: No OCT 4 positivity was found in ameloblastoma or KCOT. Ameloblastoma showed SOX 2 negativity while high SOX 2 expression was found in KCOT. Conclusion: SOX 2 is a more reliable marker for identifying stem cell population in KCOT. High expression pattern of SOX 2 in KCOT may also explain the aggressive nature of lesion and account for the presence of numerous daughter cysts responsible for its high recurrence rate, and hence, may be helpful to justify its reclassification as a tumor. Targeted therapies may be designed against these CSC populations to render more effective treatment, prevent recurrence, and reduce morbidity of the patients.