Predictors Of Malignant Transformation Research Articles

Molecular Markers in Epithelial Dysplasia as Predictors of Malignant Transformation: A Review

Abstract In the oral cavity, oncogenesis is widely believed to result from cumulative genetic alterations that cause a transformation of the mucosa from normal to dysplastic to invasive carcinoma. However, all epithelial dysplasias do not develop into cancer and some have shown to regress with time. Many potential markers have been used to diagnose the epithelial dysplasia and to predict their transformation into carcinoma such as p53 targets and family members: p53, MDM2, p16, p63, Akt. Therefore, identification of molecular and cellular markers specific to the oral lesions with potentially malignant transformation could lead to early detection, accurate diagnosis, prevention of the development of oral squamous cell carcinoma (OSCC). The present review highlights on a series of molecules markers that are reported to be significantly associated with progression of oral epithelial dysplasia to OSCC and are considered as potential biomarkers in predicting malignant transformation of epithelial dysplasias into OSCC.

Clinical parameters predictors of malignant transformation of recurrent parotid pleomorphic adenoma

Malignant transformation (MT) in recurrent parotid pleomorphic adenomas (PAs) is rare; therefore its occurrence lacks reliable predictive factors. Our goal was to clarify the predictors for MT of recurrent parotid PAs based on preoperative clinical parameters. Patients with a clinical diagnosis of recurrent parotid PA were retrospectively enrolled. The association between clinicopathologic variables and MT of PA was assessed using univariate and multivariate analyses. MT occurred in 11.8% of the 467 patients. In univariate analysis, three or more previous recurrences, newly developed facial nerve paralysis, difficulty in mouth opening, tumors with the largest tumor diameter ≥ 2.4 cm, and abnormal neck lymph node enlargement were associated with MT occurrence. Further, multivariate analysis showed that three or more previous recurrences, newly developed facial nerve paralysis, difficulty in mouth opening, and abnormal neck lymph node enlargement were independently related to MT. MT of recurrent PA was not uncommon. Clinical signs of malignancy included newly developed facial nerve paralysis, difficulty in mouth opening, three or more previous recurrences, and abnormal neck lymph node enlargement.

The Mayo Endoscopic Score Is a Novel Predictive Indicator for Malignant Transformation in Ulcerative Colitis: A Long-Term Follow-Up Multicenter Study

BackgroundData on the relative risk of malignant transformation in ulcerative colitis (UC) are insufficient. We investigated the potential value of the Mayo endoscopic score (MES) for predicting malignant transformation in patients with UC.MethodsData of patients with UC evaluated at our institute from June 1986 to December 2019 were retrospectively analyzed. The MES used in the study indicated the results of the first colonoscopy after hospitalization. We defined MES of 0–1 as low and MES of 2–3 as high. Univariable and multivariate logistic regression models were used for statistical analysis.ResultsAmong the 280 eligible patients with UC with a median follow-up time of 14 (interquartile range, 10.0–18.0) years, those with a high MES were more likely to develop malignant transformation. High MES positively correlated with the degree of malignancy and was an independent risk factor for UC-associated dysplasia and colorectal cancer (CRC, odds ratio [OR], 9.223; 95% confidence interval [CI], 1.160–73.323; p = 0.036). Disease duration >5 years (OR, 2.05; 95% CI, 1.177–3.572; p = 0.011), immunomodulator use (OR, 4.314; 95% CI, 1.725–10.785; p = 0.002), biologics nonuse (OR, 3.901; 95%CI, 2.213–6.876; p < 0.001), and Hb <90 g/L (OR, 2.691; 95% CI, 1.251–5.785; p = 0.011) were contributing factors for high MES.ConclusionHigh MES could be a novel predictor of malignant transformation in UC. Clinicians should optimize the use of biologics and immunomodulators early and should actively correct anemia to improve the MES and then reduce the incidence of UC-associated dysplasia and CRC.

Clinical Implications of the Mitotic Index as a Predictive Factor for Malignant Transformation of Atypical Meningiomas.

ObjectiveIntracranial atypical meningiomas have a poor prognosis and high rates of recurrence. Moreover, up to one-third of the recurrences undergo high-grade transformation into malignant meningiomas. We aimed to investigate the clinical factors that can predict the propensity of malignant transformation from atypical to anaplastic meningiomas. MethodsBetween 2001 and 2018, all patients with atypical meningioma, in whom the tumors had undergone malignant transformation to anaplastic meningioma, were included. The patients’ medical records documenting the diagnosis of atypical meningioma prior to malignant transformation were reviewed to identify the predictors of transformation. The control group comprised 56 patients with atypical meningiomas who were first diagnosed between January 2017 and December 2018 and had no malignant transformation. ResultsNine patients in whom the atypical meningiomas underwent malignant transformation were included. The median time interval from diagnosis of atypical meningioma to malignant transformation was 19 months (range, 7–78). The study group showed a significant difference in heterogeneous enhancement (77.8% vs. 33.9%), bone invasion (55.6% vs. 12.5%), mitotic index (MI; 14.8±4.9 vs. 3.5±3.9), and Ki-67 index (20.7±13.9 vs. 9.5±7.1) compared with the control group. In multivariate analysis, increased MI (odds ratio, 1.436; 95% confidence interval, 1.127–1.900; p=0.004) was the only significant factor for predicting malignant transformation. ConclusionAn increased MI within atypical meningiomas might be used as a predictor of malignant transformation. Tumors at high risk for malignant transformation might require more attentive surveillance and management than other atypical meningiomas.

The genetic basis of oral leukoplakia and its key role in understanding oral carcinogenesis.

Oral leukoplakia (OL) is the most common oral potentially malignant disorder, with a global prevalence of 2%-3%, variable malignant transformation rate and incompletely understood aetiology. Considering the subjectivity in oral dysplasia grading, other evaluation methods have been tested as predictors of malignant transformation. DNA ploidy status and loss of heterozygosity signatures have been shown to be good predictive markers of malignant transformation. However, effective markers to predict which lesions will progress to invasive carcinoma and by which mechanisms remain unclear. Recent evidence suggests that dysplasia progression to carcinoma occurs through neutral clonal evolution (i.e. randomly). We focus on the genetic basis of OL, encompassing the gross chromosomal alterations and single-gene mutations, and discuss such alterations in the context of aetiology, clinical presentation and progression. The deeper we understand the genetic basis of OL, the more we approach a better comprehension of the complex and poorly understood process of oral carcinogenesis.

Annual malignant transformation rate of oral leukoplakia remains consistent: A long-term follow-up study.

Numerous clinical and histopathological characteristics have been associated with malignant transformation (MT) of oral leukoplakia (OL), including classic and differentiated epithelial dysplasia, but MT predictions remain suboptimal. The objective of this study was to determine the annual MT rate of OL and to identify clinicopathological risk factors associated with MT. 170 patients with OL were included in this retrospective cohort study, 117 females and 53 males. Follow-up ranged from 12 to 219months (median 54). The analyzed variables included age, gender, smoking habits, clinical presentation, subsite, size and treatment. In a subgroup of 140 patients, histopathological diagnoses were reviewed with regard to the presence of dysplasia, discerning both classic dysplasia and differentiated dysplasia. MT occurred in 23% of the patients, resulting in an annual MT rate of 4.9% (95% CI: 3.5 - 6.6) which remained consistent. High-risk subsite (tongue and floor of mouth) was the only clinical predictor for MT (Hazard Ratio=2.7, 95% CI: 1.3 - 5.5, p=0.007). In 140 patients, classic dysplasia (Hazard Ratio=7.2, 95% CI: 1.6 - 33.1, p=0.012) and differentiated dysplasia (Hazard Ratio=6.6, 95% CI: 1.2 - 25.4, p=0.026) were predictors for MT. Binary grading between dysplasia and no dysplasia was significant for predicting MT (Hazard Ratio=6.4, 95% CI: 1.5 - 27.5, p=0.013). Since annual MT rate of OL remains stable during follow-up, regular long-term or even life-long follow-up is advocated. Specific oral subsites and epithelial dysplasia are predictors for MT of OL.

Evaluation of hematological parameters in oral cancer and oral pre-cancer

Background: Oral squamous cell carcinoma (OSCC) is the most common public health issue in Indian population. Quite a large number of OSCC cases are preceded by potentially malignant disorders of oral cavity. The need for simple diagnostic marker for early diagnosis and thus better therapeutic outcome is imperative. The current study aims to evaluate hematological parameters such as hemoglobin, bleeding time, clotting time, total leucocyte count (TLC) and differential leucocyte count (DLC) in OSCC and oral potentially malignant disorder cases along with normal healthy controls.Methods: A total of 150 subjects; 50 in each group were taken and 2.5 ml of blood were withdrawn from each subject and TLC, DLC and hemoglobin assessment was done using autoanalyzer while bleeding time and clotting time was recorded through Duke’s method and modified Dale’s method respectively.Results: All the data were tabulated and recorded as mean±standard deviation and comparison was done using one-way ANOVA test (p&lt;0.05). TLC count, neutrophil count and lymphocyte count showed statistically significant difference amongst three groups while other parameters such as hemoglobin percentage, bleeding time, clotting time, eosinophil count, monocyte count and basophil count were statistically non-significant.Conclusions: This study showed TLC count, neutrophil count and lymphocyte count might prove as useful determinant factor in oral squamous cell carcinoma and oral potentially malignant disorders. However, further study with larger sample size is required to establish their role as diagnostic, prognostic marker or predictor of malignant transformation.

Methylation silencing of TGF-\u03b2 receptor type II is involved in malignant transformation of esophageal squamous cell carcinoma

BackgroundAlthough massive studies have been conducted to investigate the mechanisms of esophageal squamous cell carcinoma (ESCC) carcinogenesis, the understanding of molecular alterations during the malignant transformation of epithelial dysplasia is still lacking, especially regarding epigenetic changes.ResultsTo better characterize the methylation changes during the malignant transformation of epithelial dysplasia, a whole-genome bisulfite sequencing analysis was performed on a series of tumor, dysplastic, and non-neoplastic epithelial tissue samples from esophageal squamous cell carcinoma (ESCC) patients. Promoter hypermethylation in TGF-β receptor type II (TGFBR2), an important mediator of TGF-β signaling, was identified. Further, we evaluated the methylation and expression of TGFBR2 in tumor samples through The Cancer Genome Atlas multiplatform data as well as immunohistochemistry. Moreover, treatment of ESCC cell lines with5-Aza-2′-deoxycytidine, a DNA methyltransferase inhibitor, reactivated the expression of TGFBR2. The lentiviral mediating the overexpression of TGFBR2 inhibited the proliferation of ESCC cell line by inducing cell cycle G2/M arrest. Furthermore, the overexpression of TGFBR2 inhibited the tumor growth obviously in vivo.ConclusionsThe characterization of methylation silencing of TGFBR2 in ESCC will enable us to further explore whether this epigenetic change could be considered as a predictor of malignant transformation in esophageal epithelial dysplasia and whether use of a TGFBR2 agonist may lead to a new therapeutic strategy in patients with ESCC.

Identification of 3 subpopulations of tumor-infiltrating immune cells for malignant transformation of low-grade glioma

BackgroundTumor-infiltrating immune cells (TIICs) are highly relevant to clinical outcome of glioma. However, previous studies cannot account for the diverse functions that make up the immune response in malignant transformation (MT) from low-grade glioma (LGG) to high-grade glioma (HGG).MethodsTranscriptome level, genomic profiles and its relationship with clinical practice were obtained from TCGA and CGGA database. The “Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)” algorithm was used to estimate the fraction of 22 immune cell types. We divided the TCGA and CGGA set into an experiment set (n = 174) and a validation set (n = 74) by random number table method. Univariate and multivariate analyses were performed to evaluate the 22 TIICs’ value for MT in LGG. ROC curve was plotted to calculate area under curve (AUC) and cut-off value.ResultsHeterogeneity between TIICs exists in both intra- and inter-groups. Several TIICs are notably associated with tumor grade, molecular subtypes and survival. T follicular helper (TFH) cells, activated NK Cells and M0 macrophages were screened out to be independent predictors for MT in LGG and formed an immune risk score (IRS) (AUC = 0.732, p < 0.001, 95% CI 0.657–0.808 cut-off value = 0.191). In addition, the IRS model was validated by validation group, Immunohistochemistry (IHC) and functional enrichment analyses.ConclusionsThe proposed IRS model provides promising novel signatures for predicting MT from LGG to HGG and may bring a better design of glioma immunotherapy studies in years to come.

ARID1A, Prostaglandin E2, and Its Receptor as Possible Predictors of Malignant Transformation of the Endometrium in Endometriosis.

We studied the expression of ARID1A, prostaglandin E2 synthase, and prostaglandin E2 receptor in the endometrium and ovarian, peritoneal, and intestinal endometrioid heterotopies in women with endometriosis of young and middle reproductive age. ARID1A protein is a tumor suppressor, its expression reduced in different types of cancer. Prostaglandin E2 synthase and prostaglandin E2 receptor are involved in the signaling cascade of inflammatory reactions presumably underlying the development of endometriosis. In endometrioid heterotopies, expression of ARID1A was reduced in 1.2-4.0 times, the expression of prostaglandin E2 synthase and prostaglandin E2 receptor was reduced in 2.9-5.2 times These findings suggest that ARID1A, prostaglandin E2 synthase, and prostaglandin E2 receptor can be used as predictors of malignant transformation of endometrioid heterotopies in women with endometriosis.

Endometriosis-assEndometriosis-associated ovarian tumors: morphological and immunohistochemical features

Background. In 2016, the World Health Organization published an updated version of the Histological Classification for ovarian tumors presenting a new category of endometriosis-associated tumors. The predictors of malignant transformation of endometriosis have not been clearly defined so far.Purpose. The search for histological and immunohistochemical markers of endometriosis-associated malignancy.Materials and methods. 28 female patients with endometrioid ovarian cancer and 11 patients with clear cell ovarian carcinoma were enrolled. Histological and immunohistochemical studies were carried out using conventional techniques. Immunohistochemistry was applied to determine the hormone receptor status: expression of steroid hormone receptors, BAF250a (ARID1A), PTEN, P-catenin, MSH6, PMS2, р-53, WT-1, proliferative index (Ki-67). Microsatellite instability (MSI) testing was conducted according to the standard protocol.Results. In all cases of ovarian cancer, histological examination showed one of the endometriosis features. Atypical endometriosis was found in 39 % (11 / 28) of endometrioid tumors and in 9% (1/ 11) of clear cell carcinomas. Endometrioid ovarian cancer was found to be ER (74±7,8%) — and PR (67±5,4%) — positive; Ki-67 index was 68,2±3,7 %; loss of BAF250a (ARID1A) expression was observed in 14% (4/ 28), loss of PTEN expression in 29 % (8 / 28), nuclear expression of P-catenin in 32% (9/28) of cases. Loss of MMR expression was detected in 7% (2/28) of cases. MSI was found in one case only, which was also associated with loss of expression of BAF250a (ARID1A) and MSH6. Clear cell carcinoma of the ovary showed histological criteria for endometriosis; however, there were no changes immunohistochemical markers expression that were typical for endometriosis-associated malignancies. It could be due to a small number of patients in the group so further research is needed.Conclusion. Atypical endometriosis may be a morphological precursor of endometrioid and clear cell carcinoma of the ovary. Comprehensive assessment of a marker panel consisting of BAF250a (ARID1A), P-catenin, PTEN, p53, Ki-67 index, PMS2 and MSH6 will allow improving the diagnosis of atypical endometriosis and endometriosis-associated ovarian cancer.

An immunohistochemical evaluation of podoplanin expression in oral leukoplakia and oral squamous cell carcinoma to explore its potential to be used as a predictor for malignant transformation.

Background:Oral leukoplakia (OL) is a potentially malignant disorder with increased risk for the development of oral squamous cell carcinoma (OSCC). Many cases of OSCC arise from the malignant transformation of preexisting OL. However, the risk of progression into OSCC and the possible prediction of malignant potential of OL remain inconclusive. Recent studies have shown that podoplanin, a mucin-like transmembrane glycoprotein specifically expressed in lymphatic endothelial cells, is expressed in various neoplasms including OSCC, indicating its possible biologic role in tumor cells. In this study, an evaluation of podoplanin expression in OL and OSCC has been carried out to assess its potential role as a biomarker to predict the possibility of malignant transformation in OL cases.Aims and Objectives:To assess the usefulness of podoplanin as a potential biomarker for predicting the risk of malignant transformation in OL, by comparing its immunohistochemical expression in OL and OSCC.Materials and Methods:Archival paraffin-embedded blocks of 25 OL cases with varying grades of dysplasia and 30 OSCC cases showing its varying grades were selected. Sections were subjected to immunohistochemical staining for podoplanin and compared with the control group for evaluation of results in the three groups.Results:A statistically significant increase in podoplanin expression was observed from normal mucosa through OL to OSCC. In the OL cases, the podoplanin staining score progressively increased from mild dysplasia to carcinoma in situ, whereas in OSCC, well-differentiated group showed the maximum expression of podoplanin.Conclusion:The progressive increase in podoplanin expression through the increasing grades of dysplasia in OL is suggestive of an increased risk for malignant transformation with increased expression of podoplanin in OL cases. A high podoplanin expression in the well-differentiated OSCC may indicate a vital role for podoplanin in the early stages of tumorigenesis.

Elevated preoperative neutrophil : lymphocyte ratio as a preoperative indicator of mature cystic teratoma with malignant transformation.

AimTo examine the usefulness of the neutrophil : lymphocyte (N/L) ratio as a cost‐effective and simple diagnostic marker of mature cystic teratoma (MCT) with malignant transformation (MT).MethodsA retrospective chart review was performed between 1998 and 2013 of 12 MCT patients with MT and between 2009 and 2013 of 130 patients with benign MCT. Data were collected on age, tumor size, white blood cell count with differential counts, tumor marker levels, and presenting features.ResultsOlder age, greater tumor size, higher CA19‐9 or CA125, higher neutrophil count, and higher N/L ratio were associated with MT on univariate analysis. White blood cell count; lymphocyte count; and the tumor marker squamous cell carcinoma antigen were not associated with MT. Older age (≥median), larger tumor size (≥10 cm), and high N/L ratio (≥5.0) were predictors of MT (hazard ratio, 11.51, 5.87, and 11.11, respectively). Six of 12 patients were diagnosed with MT on preoperative magnetic resonance imaging and five of 12 had an N/L ratio ≥5.0.ConclusionsNeutrophil : lymphocyte ratio is a potential preoperative diagnostic marker of MT. The optimal cut‐off should be determined in future large‐scale studies.

OSPs and ESPs and ISPs, Oh My! An Update on Sinonasal (Schneiderian) Papillomas.

Sinonasal (Schneiderian) papillomas are benign neoplasms that arise in the sinonasal tract. Since their initial descriptions, sinonasal papillomas have triggered debate regarding their classification, etiology, rate or predictors of malignant transformation, and other issues. While significant strides have been made in recent years, there are still aspects of sinonasal papillomas that remain unclear even now. This review will serve to update the practicing pathologist on the current understanding of sinonasal papillomas.

Radiological predictors of malignant transformation of IPMNs: importance of the predictive model validation: Author reply.

Radiological predictors of malignant transformation of IPMNs: importance of the predictive model validation: Author reply.

(Partial) Loss of BAF250a (ARID1A) in rectovaginal deep-infiltrating endometriosis, endometriomas and involved pelvic sentinel lymph nodes.

Loss of protein BAF250a (ARID1A) expression is present in women with rectovaginal deep-infiltrating endometriosis (DIE) and endometriosis affecting the pelvic sentinel lymph nodes (PSLN). Partial loss of protein BAF250a was found in some of our patient samples, comprising all endometriosis entities, including rectovaginal DIE and endometriosis affecting the PSLN. Loss of BAF250a (BRG-associated factor 250a)/ARIDIA (AT-rich interactive domain 1A) protein expression was identified among endometriosis-associated ovarian carcinomas and ovarian endometriosis, and this phenomenon was described as a possible early event in the transformation of endometriosis into cancer. DIE affecting the bowel/rectovaginal site is the most aggressive presentation of endometriosis and its 'risk' of malignant transformation has not been studied so far. We evaluated the immunohistochemical expression of BAF250a protein in 70 samples from patients enrolled in this study who were surgically treated at a tertiary center, university Hospital. The samples submitted to investigation were from rectovaginal DIE (n= 25/30), endometriosis affecting the PSLN (n= 5/7), ovarian endometriosis (n= 20/20) and endometrium from patients without endometriosis used as controls (n= 20/20). Partial loss (i.e. in one tissue section some cells stained positive for BAF250a while other cells, usually an adjacent group, were negative) of BAF250a protein was identified in 36% (9/25) of rectovaginal DIE samples, 40% (2/5) of endometriosis lesions involving the PSLN, 30% (6/20) of endometriomas, and also in 25% (5/20) of endometrium from controls. We found no statistical correlation between occurrence of partial loss of BAF250a protein and the use or not of hormone medications (P = 0.106), cycle phase (P = 0.917) and stage of disease (P = 0.717). We only found partial loss of BAF250a protein expression, and in a small population of women, with relatively high frequency in all benign tissues assessed in the present analysis. Therefore, this finding alone should not be correlated directly with the risk of malignant transformation in these lesions. The occurrence of partial loss of BAF250a protein expression in women with rectovaginal DIE and endometriosis affecting the PSLN is described for the first time. The value of this finding as a predictor of malignant transformation in endometriosis must still be clarified and further studied in association with other molecular events, such as PTEN (phosphatase and tensin homolog) deletion and PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) mutation. We might then be able to identify in the future which patients with endometriosis are at higher risk of cancer. This study was supported by an internal Charité grant to the Endometriosis Research Center and the authors declare no conflicts of interest.

Immunohistochemical expression of cyclin D1 in colorectal adenomas: a clinicopathological study

Background and objectives The colorectum is the segment of the gastrointestinal tract most frequently affected by tumors. Most colonic tumors are benign epithelial polyps. There are many histologic types of polyps. The best characterized and most common cancer precursor is the adenomatous polyp. The size, number of adenomas, grade of dysplasia, and villous features predict the future risk for advanced neoplasia, including malignancy in patients who harbor adenomas. A number of studies have been published studies evaluating the clinical use of cyclin D1 immunohistochemical (IHC) expression as a predictor of malignant transformation in colorectal adenomas. The aim of the study was to evaluate the significance of IHC expression of cyclin D1 in colorectal adenomas as a marker for the prediction of malignant transformation. Patients and methods This study is a retrospective one in which a total of 39 formalin-fixed paraffin-embedded polypectomy specimens from patients with colorectal adenomas without concurrent or previous colorectal adenocarcinoma were retrieved from the archival materials during the period from March 2013 to March 2014. The histopathological diagnosis had been revised and all specimens were stained using IHC technique with cyclin D1. Results IHC expression of cyclin D1 had a significant correlation with villous type (P=0.003) and high-grade dysplasia in adenomas (P=0.021). However, there was no significant difference in the IHC expression of cyclin D1 according to the age and sex of the patients, and the size and site of colorectal adenomas (P>0.05). Conclusion Cyclin D1 potentially contributes to the multistep process of colorectal oncogenesis. It plays an important role in the malignant conversion of colorectal adenomas, as it is more likely to be expressed in advanced adenoma with high-grade dysplasia and villous histology and can be used as an ancillary marker for the risk for malignant transformation and as a target for chemoprevention with anti-inflammatory drugs.

β-Catenin: Structure, Function and Role in Malignant Transformation of Epithelial Cells

The article presents the data on the structure and mechanisms of β-catenin functioning. The basic aspects of the role of β-catenin in malignant transformation have been studied at various tumors. Primary structure of β-catenin allows it to interact with many factors and ligands, including transcription factors, α-catenin, cadherin, Axin, Rho family GTPases, Bcl9 et al. This interaction is the base for β-catenin's intracellular multi-functioning. The review presents data on the participation of β-catenin in the mechanisms of adhesion, regulation of RNA metabolism, formation contacts with the cytoskeleton and its role in the canonical Wnt signaling pathway, marked examples pro-inflammatory and anti-inflammatory effects of β-catenin. The β-catenin involvement in malignant transformation and progression of certain tumors is not in doubt. The data on the changes in β-catenin expression in the given examples of colon cancer, prostate cancer, different forms of thyroid cancer and hepatocellular carcinoma are presented with the prospects of its use as a marker and a predictor of malignant transformation. Continued research in this area will not only make use of β-catenin as a potential predictor of malignant tumors, but also to develop approaches to targeted therapy.

Predictive factors for the presence of malignant transformation of pelvic endometriosis

Abstract Objectives To determine predictive factors for the presence of malignant transformation in ovarian endometriotic cysts. Study design This was an IRB approved, case control study analyzing patient data from 2004 to 2013. Pathology database records were searched to identify patients with benign endometrioma and ovarian carcinoma arising in the background of endometriosis. Inclusion criteria required each patient to have a preoperative diagnosis of adnexal mass and no other findings concerning for malignancy. Patient clinical records were queried for preoperative symptoms, serum CA125 levels and radiologic findings. Pathologic data were collected including histology, tumor grade and stage. Results A total of 138 patients met inclusion criteria; 42 women with ovarian cancer arising in the background of endometriosis and 96 women with benign endometrioma. Women diagnosed with ovarian cancer were significantly older than women with endometriosis (53.6 vs. 39.2 years). There was no difference in presence of symptoms between the two groups. Women with malignant tumors were found to have significantly larger cysts (14cm vs. 7.5cm; p p p p =0.02). Multiple logistic regression analysis indicated that for every 5 years increase in age there was an adjusted OR of 2.17 ( p =0.003). An age of 49 years or greater had an 80.6% sensitivity (95% CI: 62.5–92.5%) and an 82.9% specificity (95% CI: 67.9–92.8%) for malignancy, and solid component on imaging had an adjusted OR of 23.7 ( p p =0.1). Conclusions Significant predictors for malignant transformation of endometriosis include cyst characteristics and age. Women above the age of 49 with multilocular cysts and solid components are at high risk for malignant transformation of endometriosis. Serum CA125 level is not a significant predictor of malignant transformation.

Immunohistochemical evaluation of oral epithelial dysplasia using cyclin-D1, p27 and p63 expression as predictors of malignant transformation.

Objective:To evaluate the degree of expression of cyclin-D1, p27 and p63 in mild, moderate and severe dysplasia using immunohistochemical evaluation in order to illustrate their prognostic value and attempt to propose a molecular grading system for oral epithelial dysplasia.Materials and Methods:The analysis included thirty cases of mild, moderate and severe dysplasia from Department of Oral and Maxillofacial Pathology, Saveetha Dental College, Chennai after a critical review of the Hematoxylin and Eosin (H and E) stained sections. They were subjected to immunohistochemical evaluation using the markers cyclin-D1, p27 and p63. The assessment of the expression based on staining intensity and distribution of immunohistochemical staining of the various markers was analyzed followed by statistical analysis.Results:A highly significant increase in the expression of cyclin-D1 (P < 0.000) and p63 (P < 0.001) and a moderately significant decrease in the expression of p27 (P < 0.012) with the increasing severity of dysplasia was observed in our study.Conclusions:The result of our research affirms the fact that the increase in the expression of markers of cell cycle regulators such as cyclin D1, decrease in the expression of cell cycle inhibitors like p27 and increased expression of p63 in parallel with the increasing severity of dysplasia, emphasizes the use of immunohistochemical markers cyclin D1, p27 and p63 as prognostic markers for better understanding the behaviour of these potentially malignant disorders aiming towards proposing a molecular grading system for oral epithelial dysplasia to enable timely management prior to their possible malignant transformation.