In vivo imaging of oral neoplasia using a miniaturized fiber optic confocal reflectance microscope

The purpose of this study was to determine whether in vivo images of oral mucosa obtained with a fiber optic confocal reflectance microscope could be used to differentiate normal and neoplastic tissues. We imaged 20 oral sites in eight patients undergoing surgery for squamous cell carcinoma. Normal and abnormal areas within the oral cavity were identified clinically, and real-time videos of each site were obtained in vivo using a fiber optic confocal reflectance microscope. Following imaging, each site was biopsied and submitted for histopathologic examination. We identified distinct features, such as nuclear irregularity and spacing, which can be used to qualitatively differentiate between normal and abnormal tissue. Representative confocal images of normal, pre-neoplastic, and neoplastic oral tissue are presented. Previous work using much larger microscopes has demonstrated the ability of confocal reflectance microscopy to image cellular and tissue architecture in situ. New advances in technology have enabled miniaturization of imaging systems for in vivo use.     

Confocal microscopy and molecular-specific optical contrast agents for the detection of oral neoplasia

Using current clinical diagnostic techniques, it is difficult to visualize tumor morphology and architecture at the cellular level, which is necessary for diagnostic localization of pathologic lesions. Optical imaging techniques have the potential to address this clinical need by providing real-time, sub-cellular resolution images. This paper describes the use of dual mode confocal microscopy and optical molecular-specific contrast agents to image tissue architecture, cellular morphology, and sub-cellular molecular features of normal and neoplastic oral tissues. Fresh tissue slices were prepared from 33 biopsies of clinically normal and abnormal oral mucosa obtained from 14 patients. Reflectance confocal images were acquired after the application of 6% acetic acid, and fluorescence confocal images were acquired after the application of a fluorescence contrast agent targeting the epidermal growth factor receptor (EGFR). The dual imaging modes provided images similar to light microscopy of hematoxylin and eosin and immunohistochemistry staining, but from thick fresh tissue slices. Reflectance images provided information on the architecture of the tissue and the cellular morphology. The nuclear-to-cytoplasmic (N/C) ratio from the reflectance images was at least 7.5 times greater for the carcinoma than the corresponding normal samples, except for one case of highly keratinized carcinoma. Separation of carcinoma from normal and mild dysplasia was achieved using this ratio (p<0.01). Fluorescence images of EGFR expression yielded a mean fluorescence labeling intensity (FLI) that was at least 2.7 times higher for severe dysplasia and carcinoma samples than for the corresponding normal sample, and could be used to distinguish carcinoma from normal and mild dysplasia (p<0.01). Analyzed together, the N/C ratio and the mean FLI may improve the ability to distinguish carcinoma from normal squamous epithelium.     

Understanding the biological basis of autofluorescence imaging for oral cancer detection: high-resolution fluorescence microscopy in viable tissue.

PURPOSE: Autofluorescence imaging is increasingly used to noninvasively identify neoplastic oral cavity lesions. Improving the diagnostic accuracy of these techniques requires a better understanding of the biological basis for optical changes associated with neoplastic transformation in oral tissue. EXPERIMENTAL DESIGN: A total of 49 oral biopsies were considered in this study. The autofluorescence patterns of viable normal, benign, and neoplastic oral tissue were imaged using high-resolution confocal fluorescence microscopy. RESULTS: The autofluorescence properties of oral tissue vary significantly based on anatomic site and pathologic diagnosis. In normal oral tissue, most of the epithelial autofluorescence originates from the cytoplasm of cells in the basal and intermediate regions, whereas structural fibers are responsible for most of the stromal fluorescence. A strongly fluorescent superficial layer was observed in tissues from the palate and the gingiva, which contrasts with the weakly fluorescent superficial layer found in other oral sites. Upon UV excitation, benign inflammation shows decreased epithelial fluorescence, whereas dysplasia displays increased epithelial fluorescence compared with normal oral tissue. Stromal fluorescence in both benign inflammation and dysplasia drops significantly at UV and 488 nm excitation. CONCLUSION: Imaging oral lesions with optical devices/probes that sample mostly stromal fluorescence may result in a similar loss of fluorescence intensity and may fail to distinguish benign from precancerous lesions. Improved diagnostic accuracy may be achieved by designing optical probes/devices that distinguish epithelial fluorescence from stromal fluorescence and by using excitation wavelengths in the UV range.     

Toward a multimodal cell analysis of brush biopsies for the early detection of oral cancer

BACKGROUND:

This report describes what to the authors' knowledge is the first clinical application of semiautomated multimodal cell analysis (MMCA), a novel technique for the early detection of cancer for cases with a limited number of suspicious cells. In this clinical study, MMCA was applied to oral cancer diagnostics on brush biopsies. The MMCA approach was based on the sequential application of multiple stainings of identical, slide‐based cells and repeated relocalizations and measurements of their diagnostic features, resulting in multiparametric features of individual cells. Data integration of the variously stained cells increased diagnostic accuracy. The implementation of MMCA also enabled fully automatic, adaptive image preprocessing, including registration of multimodal images and segmentation of cell nuclei.

METHODS:

In a preliminary clinical trial, 47 slides from brush biopsies of suspicious oral lesions were analyzed. The final histologic diagnoses included 20 squamous cell carcinomas, 7 hyperkeratotic leukoplakias, and 20 lichen planus mucosae.

RESULTS:

The stepwise application of 2 additional approaches (morphology, DNA content, argyrophilic nucleolar organizer region counts) increased the specificity of conventional cytologic diagnosis from 92.6% to 100%. This feasibility study provided a proof of concept, demonstrating efficiency, robustness, and diagnostic accuracy on slide‐based cytologic specimens.

CONCLUSIONS:

The authors concluded that MMCA may become a sensitive and highly specific, objective, and reproducible adjuvant diagnostic tool for the identification of neoplastic changes in oral smears that contain only a few abnormal cells. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues

This study characterizes the morphologic features and the endogenous fluorescence in the stratified squamous epithelia of the 7,12-dimethylbenz(a)anthracene-treated hamster cheek pouch model of carcinogenesis using multiphoton laser scanning microscopy (MPLSM). MPLSM allows high-resolution, three-dimensional image data to be collected deeper within thick tissue samples with reduced phototoxicity compared with single-photon imaging. Three-dimensional image stacks of normal (n = 13), precancerous (dysplasia, n = 12; carcinoma in situ, n = 9) and cancerous tissue [nonpapillary squamous cell carcinoma (SCC), n = 10, and papillary SCC, n = 7] sites in the hamster cheek pouch were collected in viable, unsectioned tissue biopsies at a two-photon excitation wavelength of 780 nm. Five features were quantified from the MPLSM images. These included nuclear density versus depth, keratin layer thickness, epithelial thickness, and the fluorescence per voxel in the keratin and epithelial layers. Statistically significant differences in all five features were found between normal and both precancerous and cancerous tissues. The only exception to this was a lack of statistically significant differences in the keratin fluorescence between normal tissues and papillary SCCs. Statistically significant differences were also observed in the epithelial thickness of dysplasia and carcinoma in situ, and in the keratin layer thickness of dysplasia and SCCs (both nonpapillary and papillary). This work clearly shows that three-dimensional images from MPLSM of endogenous tissue fluorescence can effectively distinguish between normal, precancerous, and cancerous epithelial tissues. This study provides the groundwork for further exploration into the application of multiphoton fluorescence endoscopy in a clinical setting.     

Reduced E-cadherin expression is an indicator of unfavourable prognosis in oral squamous cell carcinoma

The aim was to evaluate E-cadherin expression in oral squamous cell carcinoma, and its possible relationships with tumour histology and with clinical course and survival. Surgical biopsies from 47 cases of oral squamous cell carcinoma were analysed for expression of E-cadherin using immunohistochemistry. Statistical analyses were performed to identify possible associations with tumour clinic-histological features and with clinical course and survival. Weak or absent E-cadherin expression was associated with a more invasive histological pattern and with metastasis to the cervical lymph nodes. Uni- and multivariate analyses indicated that weak or undetectable E-cadherin expression is an indicator of shorter disease-free period and shorter survival time. Reduced E-cadherin expression in oral squamous cell carcinoma is associated with more aggressive tumour behaviour and worse prognosis.     

Image cytometry DNA analysis of invasive squamous cell carcinoma of the esophagus

The Feulgen-DNA content of squamous carcinoma cell nuclei from the human esophagus was assessed in punch biopsies from 47 untreated patients. Forty-four of the 47 biopsies (93.6%) demonstrated aneuploid cell populations, and the remaining 3 (6.4%) were non-diploid. Previous studies have demonstrated that in esophageal dysplasias adjacent to invasive squamous cell carcinoma, DNA in single cells is substantially altered. Thus the process of esophageal carcinogenesis can be monitored not only by histological changes, but also by DNA aberrations in single cells. Quantitative DNA measurement appears, therefore, to be a complement to the histological evaluation of esophageal lesions with suspected, but not unequivocal, evidence of neoplastic growth.     

Confocal endomicroscopic imaging of normal and neoplastic human tongue tissue using ALA-induced-PPIX fluorescence: a preliminary study

Confocal endomicroscopy is a novel and non-invasive microscopic technique that enables surface and subsurface imaging of living tissues or cells in vivo. The purpose of this study was to assess the possibility of utilizing a rigid confocal endomicroscope (RCE) system developed for detecting morphological changes in living normal and neoplastic human tongue tissue in combination with 5-aminolevulinic acid (ALA)-induced endogenous protoporphyrin IX (PPIX) fluorescence. Three patients with squamous cell carcinoma (SCC) of the tongue were examined using the novel RCE system with the excitation wavelength at 488 nm from an argon-ion laser and the detection wavelengths of the tissue fluorescence above 515 nm. Patients were topically applied with 0.4% of 5-ALA rinsing solution to the oral mucosa for approximately 15 min, and then the confocal endomicroscopic imaging of tissue PPIX fluorescence was performed on the lesion sites of the tongue after an optimal incubation period of 90-120 min. For comparison purposes, ALA-PPIX fluorescence confocal endomicroscopic imaging was also carried out on the normal sites of the tongue in vivo from two healthy volunteers. Image distortions due to tissue motion can be minimized using a specially designed tissue stabilizer attached to the RCE probe. Good quality ALA-mediated confocal fluorescence images of the tongue can be acquired in real-time, providing well-defined micro-morphological structures (e.g., filiform papillae, keratinized epithelium and fungiform papillae) of the tongue in vivo. Changes of tissue structures in oral tissue associated with cancer transformation can also be clearly identified using the RCE imaging. Preliminary results obtained in this study suggest that ALA-mediated rigid confocal endomicroscopy may have a significant potential for the rapid, non-invasive diagnosis and evaluation of early oral cancers in vivo.     

Orthogonal polarization spectral (OPS) imaging and topographical characteristics of oral squamous cell carcinoma

Tumor microcirculatory characteristics until now have only been assessed by histological examination of biopsies or invasive imaging technique. The recent introduction of orthogonal polarization spectral (OPS) imaging as a new tool for in vivo visualization of human microcirculation makes it possible to acquire high resolution images of the oral mucosa. In this study we report the microcirculatory changes in ten patients with oral squamous cell carcinoma of the tongue and compared the images to the normal contralateral side as the control. All carcinomas were T2 tumors without evidence for lymph node metastasis. The carcinomas were characterized by chaotic and dilated vessels accompanied by numerous areas of haemorrhage. The OPS technique seems very promising in the assessment of oral squamous cell carcinoma microcirculatory characteristics and may possibly play a future role in both the detection of early oral mucosal vascular aberrations and the effect of anti-tumor agents on the tumor microvasculature.     

Potential use of quantitative tissue phenotype to predict malignant risk for oral premalignant lesions

The importance of early diagnosis in improving mortality and morbidity rates of oral squamous cell carcinoma (SCC) has long been recognized. However, a major challenge for early diagnosis is our limited ability to differentiate oral premalignant lesions (OPL) at high risk of progressing into invasive SCC from those at low risk. We investigated the potential of quantitative tissue phenotype (QTP), measured by high-resolution image analysis, to identify severe dysplasia/carcinoma in situ (CIS; known to have an increased risk of progression) and to predict progression to cancer within hyperplasia or mild/moderate dysplasia. We generated a nuclear phenotype score (NPS), a combination of five nuclear morphometric features that best discriminate 4,027 "normal" nuclei (selected from 29 normal oral biopsies) from 4,298 "abnormal" nuclei (selected from 30 SCC biopsies). This NPS was then determined for a set of 69 OPLs. Severe dysplasia/CIS showed a significant increase in NPS compared with hyperplasia or mild/moderate dysplasia. However, within the latter group, elevated NPS was strongly associated with the presence of high-risk loss of heterozygosity (LOH) patterns. There was a statistical difference between NPS of hyperplasia or mild/moderate dysplasia that progressed to cancer and those that did not. Individuals with a high NPS had a 10-fold increase in relative risk of progression. In the multivariate Cox model, LOH and NPS together were the strongest predictors for cancer development. These data suggest that QTP could be used to identify lesions that require molecular evaluation and should be integrated with such approaches to facilitate the identification of hyperplasia or mild/moderate dysplasia OPLs at high risk of progression.     

Differential expression of the non-receptor tyrosine kinase BRK in oral squamous cell carcinoma and normal oral epithelium

BRK is a non-receptor tyrosine kinase whose functional role is poorly understood. Although it is an epithelial specific kinase, its expression appears to be tissue specific. To date, little is known about BRK expression in human oral epithelium. We investigated expression of BRK in human oral squamous cell carcinomas (OSCC) and normal oral epithelium (NOE) using immunohistochemistry, laser confocal microscopy and Western blotting. The subcellular localization of BRK was identified by confocal microscopy and Western blotting of nuclear and cytoplasmic extracts from these cells. The results indicate that NOE express higher levels of BRK compared with OSCC cells. In NOE and moderately differentiated OSCC cells, BRK was localized in the nucleus and cytoplasm. However, in poorly differentiated OSCC cells, BRK was localized in perinuclear regions. These results suggest that BRK expression differs in normal and OSCC which may reflect a possible functional involvement in OSCC.     

Basaloid squamous carcinoma of oral cavity: a histologic and immunohistochemical study

Basaloid squamous carcinoma (BSC) is an aggressive variant of squamous cell carcinoma (SCC) with a predilection for the upper aerodigestive tract. In the English literature, approximately 40 cases of BSC have been described in the oral cavity. BSC has frequently been confused with adenoid cystic carcinoma (ACC), basal cell adenocarcinoma, and undifferentiated SCC. The purpose of the investigation was to examine the histological features and immunohistochemical expression of differentiation-related substances, including cytokeratin (CK) subtypes, vimentin, S-100, chromogranin, laminin, and type IV collagen, for the characterization of biological features of these tumours. We studied three cases of BSC of the oral cavity, three cases of ACC, and one case of basal cell adenocarcinoma. Well-differentiated and undifferentiated SCCs were also studied for comparison. The BSCs showed many histopathologic similarities to cases previously reported. Among the CK subtypes analyzed, CK14 was the only subtype expressed by all basaloid cells of BSC. Potentially useful for the differential diagnosis was the finding of CKs 7 and 19 expression in the basaloid cells of ACC, and CKs 7 and 8 in basal cell adenocarcinoma. In BSCs, laminin and type IV collagen were found in the microcystic spaces between basaloid cells, but neither ACCs nor basal cell adenocarcinoma showed this feature. These data suggest that immunohistochemical findings are helpful in distinguishing BSC of the oral cavity from other histopathologically similar tumours.     

唇癌及口腔癌调强放疗失败的临床研究

目的：探讨唇部及口腔鳞状细胞癌调强放疗失败的原因。方法：55例唇部及口腔鳞状细胞癌患者接受调强放疗，其中49例为术后放疗，5例为根治性放疗，1例为新辅助放疗。通过复发时CT图像与治疗计划用CT图像的融合或对比来判断复发方式。结果：9例患者出现局部区域复发：4例仅有局部复发，2例仅有区域复发，3例局部＋区域复发。5例患者出现远处转移，其中3例合并局部区域复发。2年总生存率、疾病特异性生存率、局部无复发生存率、局部区域无复发生存率、以及远处无转移生存率分别为68％、74％、85％、82％和89％。从治疗结束到局部区域复发的中位时间为4．1个月。除1例失败出现在照射野外的对侧下颈部外，其余的失败都出现在接受高量放疗的部位。局部区域控制与淋巴结包膜外侵显著相关。结论：调强放疗是唇部及口腔鳞状细胞癌的有效治疗方式。绝大多数治疗失败的方式为“照射野内”复发，建议术后同步化放疗用于有淋巴结包膜外侵的唇癌及口腔癌患者。     

Nuclear fractal dimension as a prognostic factor in oral squamous cell carcinoma

Strong theoretical reasons exist for using fractal geometry in measurements of natural objects, including most objects studied in pathology. Indeed, fractal dimension provides a more precise and theoretically more appropriate approximation of their structure properties and especially their shape complexity. The aim of our study was to evaluate the nuclear fractal dimension (FD) in tissue specimens from patients with oral cavity carcinomas in order to assess its potential value as prognostic factor. Relationships between FD and other factors including clinicopathologic characteristics were also investigated. Histological sections from 48 oral squamous cell carcinomas as well as from 17 non-malignant mucosa specimens were stained with Hematoxylin-Eosin for pathological examination and with Feulgen for nuclear complexity evaluation. The sections were evaluated by image analysis using fractal analysis software to quantify nuclear FD by the box-counting method. Carcinomas presented higher mean values of FD compared to normal mucosa. Well differentiated neoplasms had lower FD values than poorly differentiated ones. FD was significantly correlated with the nuclear size. Patients with FD lower than the median value of the sample had statistically significant higher survival rates. Within the sample of patients studied, FD was proved to be an independent prognostic factor of survival in oral cancer patients. In addition this study provides evidence that there are several statistically significant correlations between FD and other morphometric characteristics or clinicopathologic factors in oral squamous cell carcinomas.     

STAT1 activation in squamous cell cancer of the oral cavity: a potential predictive marker of response to adjuvant chemotherapy

BACKGROUND: For patients with squamous cell carcinoma of the oral cavity, both locoregional and distant recurrences are common, and an appropriate adjuvant treatment modality has yet to be defined. Thus, there is an urgent need to identify novel molecular markers with potential prognostic and/or predictive value to improve treatment outcome in these patients. This retrospective study was designed to investigate the predictive and/or prognostic value of STAT1 activation in squamous cell carcinoma of the oral cavity. METHODS: STAT1 expression and subcellular localization was examined immunohistochemically on a tissue microarray of paraffin-embedded tumor specimens from 89 patients who underwent surgical treatment in the period between 1980 and 1997. A nuclear staining score of greater than 35% was defined as high STAT1 activation. RESULTS: According to study criteria, 18% of analyzed tumor samples exhibited high STAT1 activation. High STAT1 activation was associated with negative lymph node status. Moreover, in the subgroup of patients who received chemotherapy, high nuclear STAT1 staining in the tumor was associated with good prognosis. CONCLUSIONS: This is the first report demonstrating the potential predictive value of STAT1 activation status in patients with squamous cell cancer of the oral cavity. If confirmed in large prospective trials, this molecular marker could help in guiding therapeutic decisions in these patients.     

Quantitation of chromatin patterns by image analysis as a predictive tool in chemopreventive trials with vitamin A

Nuclear textures of oral mucosal cells were quantitated by image analysis, and their suitability as markers in a chemopreventive trial explored. Subjects were chewers of tobacco-containing betel quids with well established oral leukoplakias. Treatment consisted of a weekly oral administration of vitamin A (200,000 IU/week) for six months. Leukoplakias regressed in 57.1% of the 21 trial participants. The original leukoplakias did not redevelop within four months after termination of treatment. For image analysis, biopsies were taken from leukoplakias of five chewers before administration of vitamin A, at the end of the administration, and four months after termination of treatment. Sections of paraffin-embedded biopsies were stained with the Feulgen reaction and submitted to quantitative image analysis of two parameters: variance of intensity and entropy. Both these parameters were significantly reduced in all five trial participants as a result of the six-month vitamin A treatment. During the post-treatment period, nuclei with condensed chromatin, as measured by the variance of intensity, reappeared in the mucosa of four of the five chewers examined, although no leukoplakias were detectable on visual examination of the oral cavity. The results indicate that the quantitation of nuclear textures in a small subpopulation of a chemopreventive trial could conceivably be a simple marker with a predictive value.     

Field cancerization in oral lichen planus.

BACKGROUND: The concept of field cancerization describes the tendency of patients with premalignant and malignant lesions of head and neck mucosal sites to develop multiple carcinomas of the upper aerodigestive tract. Here we address whether this concept should be extended also to patients affected by oral lichen planus (OLP), an inflammatory disorder associated with an increased risk of cancer development. METHODS: Data from a cohort of 45 patients with OLP who subsequently developed severe dysplastic changes and/or oral squamous cell carcinoma were retrospectively reviewed. Patients who presented more than one oral neoplastic event were considered for further data analysis as regards incidence, localization, management and prognosis. RESULTS: Twenty (44.4%) patients were affected by one single neoplastic event while 25 (55.6%) developed multiple and often multifocal oral dysplastic and/or malignant events. In most cases, a careful surveillance programme led to diagnosis and effective treatment of oral neoplasias at an early intraepithelial and microinvasive stage, leading to long-term survival. In some patients, however, additional primary tumours occurred suddenly with rapid invasion, leading to advanced stage diagnosis and poor prognosis. Overall, three patients (12%) died due to malignant oral disease. CONCLUSIONS: Patients with OLP and subsequent development of dysplasia/ oral squamous cell carcinoma are at risk of having multiple and multifocal neoplastic events of the oral cavity, a phenomenon which parallels the concept of field cancerization of traditional head and neck cancers. If detected at an early stage, these neoplasias can be managed with superficial and complete resection. However a small number of patients have loco-regional tumour spread despite a standard surveillance protocol.     

Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ

Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer‐associated adipocytes, undergo extensive changes that correspond to an “activated phenotype,” such as reduced size relative to adipocytes in non‐neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non‐neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions.     

宫颈液基细胞学中非典型腺细胞的形态结构特征与临床意义

目的:探讨宫颈液基细胞学中非典型腺细胞诊断的临床意义,评估有临床意义的细胞学形态结构特征,研究细胞学中鉴别腺上皮细胞病变与鳞状细胞病变的形态线索。方法:对我院2011年至2019年液基细胞学筛查为非典型腺细胞(atypical glandular cell, AGC)的病例复阅,通过与组织学结果对照,评估相关的细胞学特征。结果:514例AGC患者中,组织学结果阳性232例(45.1%),包括腺细胞病变114例(22.2%),鳞状上皮细胞病变104例(20.2%),腺细胞病变合并鳞状上皮细胞病变11例(2.1%),其他恶性肿瘤3例(0.6%)。评估的11个细胞学特征中,有8个特征在良性变化和癌或癌前病变之间有显著的统计学差异(P<0.05),分别为失去极性、羽毛状结构、乳头样结构、核膜不规则、出现大核仁、粗糙的染色质、中性粒细胞口袋、细胞浆内大空泡。有6个与腺上皮病变相关,前3位依次是：中性粒细胞口袋、羽毛状结构、细胞浆内大空泡;有4个与鳞状上皮病变相关,前3位分别是：核膜不规则、核深染、粗糙的染色质;羽毛状结构对于区别腺上皮病变和鳞状上皮病变最有意义。结论:AGC随访恶性率高,细...     

Immunohistochemical Expression of Cyclin D1 and Ki-67 in Primary and Metastatic Oral Squamous Cell Carcinoma

Objective: The aim of current study was to investigate the expression of Cyclin D1 and Ki-67 in primary and metastatic oral squamous cell carcinoma (OSCC) and their different histological grades. Methods: Paraffin embedded 30 oral squamous cell carcinoma (15 each of primary and cervical lymph node metastatic OSCC) were included in the study. Cyclin D1 and Ki 67 expressions were evaluated by immunohistochemistry and compared in primary and lymph node metastasis of OSCC and their histological grades. The data was analyzed using SPSS software. Results: The mean age of patients with primary OSCC was 53.47 ±16.67 years and 61.47 ±11.94 years in patients with metastasis. Males were comparatively affected more than females with tongue as the most common site involved in both primary and metastatic tumours. The mean size of primary and metastatic tumour biopsies were 1.16 mm and 3.93 mm respectively. Comparison of the expression of Cyclin D1 in these primary and metastatic OSCC revealed a statistically significant difference (p = 0.003) whereas it was insignificant for Ki-67 (p = 0.715). Conclusion: Cyclin D1 can be a useful marker in predicting aggressive or metastatic behaviour of OSCC on premier biopsies.