Marker For Adenoid Cystic Carcinoma Research Articles

EXPRESSION OF MITOCHONDRIAL DYNAMIC MARKERS IN ADENOID CYSTIC CARCINOMA

Objective This study aimed to investigate the prognostic significance of mitochondrial dynamic markers in adenoid cystic carcinoma (AdCC). Study Design Fifty-seven formalin-fixed paraffin-embedded cases were retrieved and disposed in a tissue microarray. Histological sections were submitted to immunohistochemical reactions against AMT, DRP1, FIS1, MFN1, MFN2, and OPA1 proteins. Clinical data were retrieved from the patients’ medical files, including specific and disease-free survival data. Results It was observed that 50.9% of the cases were strongly positive for AMT and DRP1, while 49.1%, 21.1%, 22.8%, and 24.6% were strongly positive for FIS1, MFN1, MFN2, and OPA1, respectively. Reactions were observed in both epithelial and myoepithelial components of the tumor. The higher expression of MFN2 was associated with a solid microscopic pattern (p = .016). DRP1 overexpression showed a trend towards a shorter overall survival (p = .054), while negative/weak OPA1 showed a trend towards a lower DFS (p=.051) in the univariate analysis, but no mitochondrial marker represented an independent prognostic determinant under multivariate analysis. Conclusion Mitochondrial dynamics markers do not seem to carry a prognostic significance for AdCC patients, but these proteins may play an important role in its pathogenesis. Support: FAPEMIG, CAPES, CNPq. This study aimed to investigate the prognostic significance of mitochondrial dynamic markers in adenoid cystic carcinoma (AdCC). Fifty-seven formalin-fixed paraffin-embedded cases were retrieved and disposed in a tissue microarray. Histological sections were submitted to immunohistochemical reactions against AMT, DRP1, FIS1, MFN1, MFN2, and OPA1 proteins. Clinical data were retrieved from the patients’ medical files, including specific and disease-free survival data. It was observed that 50.9% of the cases were strongly positive for AMT and DRP1, while 49.1%, 21.1%, 22.8%, and 24.6% were strongly positive for FIS1, MFN1, MFN2, and OPA1, respectively. Reactions were observed in both epithelial and myoepithelial components of the tumor. The higher expression of MFN2 was associated with a solid microscopic pattern (p = .016). DRP1 overexpression showed a trend towards a shorter overall survival (p = .054), while negative/weak OPA1 showed a trend towards a lower DFS (p=.051) in the univariate analysis, but no mitochondrial marker represented an independent prognostic determinant under multivariate analysis. Mitochondrial dynamics markers do not seem to carry a prognostic significance for AdCC patients, but these proteins may play an important role in its pathogenesis. Support: FAPEMIG, CAPES, CNPq.

Expression of mitochondrial dynamic markers in adenoid cystic carcinoma.

Mitochondrial fission and fusion processes are known as mitochondrial dynamics and the occurrence of imbalances in the mitochondrial activity is related to the pathogenesis of many human cancers. However, the importance of mitochondrial dynamics in malignant salivary gland tumours remains unknown. Therefore, we aimed to investigate its prognostic significance in adenoid cystic carcinoma. Fifty-seven formalin-fixed paraffin-embedded cases were retrieved and disposed in tissue microarray. Histological sections were submitted to immunohistochemical reactions against AMT, DRP1, FIS1, MFN1, MFN2 and OPA1 proteins. Clinical data were retrieved from the patients' medical files, including specific and disease-free survival data. It was observed that 50.9% of the cases were strongly positive for AMT and DRP1, and 49.1%, 21.1%, 22.8% and 24.6% strongly positive for FIS1, MFN1, MFN2 and OPA1, respectively. Reactions were observed in both epithelial and myoepithelial components of the tumour. The higher expression of MFN2 was associated with solid microscopic pattern (p=0.016). DRP1 overexpression showed a trend towards a shorter overall survival (p=0.054), while negative/weak OPA1 showed a trend towards a lower disease-free survival (p=0.051) in the univariate analysis, but no mitochondrial marker represented an independent prognostic determinant under multivariate analysis. In conclusion, mitochondrial dynamics markers do not seem to carry a prognostic significance for adenoid cystic carcinoma patients, but these proteins may play an important role in its pathogenesis.

Prognostic Relevance of Thyroid-Hormone-Associated Proteins in Adenoid Cystic Carcinoma of the Head and Neck.

The proteins sodium iodide symporter (NIS), μ-crystallin (CRYM), and thyroid hormone receptor beta (THRB) have been associated with prognosis in various cancer entities. While NIS and THRB may serve as possible therapeutic targets, the role of CRYM in cancer is still unclear. Protein levels of 44 patients with adenoid cystic carcinoma of the head and neck were analyzed using immunohistochemistry and correlated with clinicopathological data and outcome. NIS was positive in 72%, CRYM was positive in 55%, and THRB was positive in 39% of the patients. CRYM-positive adenoid cystic carcinomas were associated with a better cause-specific survival. Thus, our data indicate that CRYM might be a suitable positive prognostic marker in adenoid cystic carcinoma of the head and neck. Furthermore, expression of NIS was present in most patients and therefore evaluation of the use of radioiodine treatment is recommended.

Homeobox transcription factor engrailed homeobox 1 is a possible diagnostic marker for adenoid cystic carcinoma and polymorphous adenocarcinoma.

Diagnostic utility of a homeobox transcription factor, engrailed homeobox 1 (En1) in the histopathology of salivary gland neoplasms was studied. The expression of En1 was immunohistochemically examined in 51 cases of adenoid cystic carcinoma (AdCC) and 143 cases of other salivary gland neoplasms. In all 51 AdCCs, En1 was expressed in 30-100% of tumor cells. In eight of nine polymorphous adenocarcinomas (PACs), En1 was expressed in 40-100% of tumor cells. Less than 5% of tumor cells expressed En1 in three of 12 epithelial-myoepithelial carcinomas, one of 17 basal cell adenomas (BCAs), and one of 34 pleomorphic adenomas (PAs). Among 55 other carcinoma cases, 1-30% of tumor cells expressed En1 in three salivary duct carcinomas (SDCs) ex PA. None of the myoepitheliomas and Warthin tumors expressed En1. When the cut-off value of the percentage of En1-expressing cells was set to 25%, all 51 AdCCs, eight of nine PACs and one SDC ex PA were En1-positive and the others were En1-negative. En1 is expressed consistently in AdCCs, frequently in PACs, but rarely in other salivary gland neoplasms. En1 is a possible diagnostic marker for AdCC and PAC in the histopathology of salivary gland neoplasms.

The value of MYB as a prognostic marker for adenoid cystic carcinoma: Meta‐analysis

The aim of this meta-analysis is to evaluate myeloblastosis (MYB) as a prognostic marker for patients with adenoid cystic carcinoma (ACC) with respect to MYB gene fusion, MYB protein expression, and tumor sites. We comprehensively searched PubMed, Embase, Web of Science, and Cochrane libraries. Ten studies concerning the prognostic comparisons between MYB positivity and negativity were included. The combined positive rates of MYB gene fusion and protein expression were 57.2% and 62.3%, respectively. Overall, no significant prognostic differences were observed between MYB-positive and MYB-negative ACCs. When further divided into MYB gene fusion and MYB protein expression subgroups, no significant differences were observed for any survival outcome (overall survival, disease-free survival, and local control rate). Moreover, MYB also demonstrated no prognostic value in head and neck ACCs. In conclusion, the current studies reveal that MYB is not a good prognostic marker for ACC.

Pretreatment assessment of hematologic and inflammatory markers in adenoid cystic carcinoma: neutrophil/lymphocyte ratio is associated with multiple recurrences

Adenoid cystic carcinoma (ACC) is a rare entity of salivary gland cancer. Inflammatory and hematologic markers and their prognostic and predictive value have been intensively studied in several cancer entities. The aim of this study was to investigate the role of such markers in patients with ACC. This retrospective analysis investigated hematologic and inflammatory markers in patients with ACC in the period between the years 1996 and 2016. We assessed the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, cross-reactive protein and fibrinogen levels. A total of 28 to 31 patients were included, depending on the examined parameter. All markers were evaluated for their effects on outcome and prognostic value. Patients with an elevated preoperative NLR (>2) had a significantly higher multiple recurrence rate (44.4% vs 8.3%; P = .049). Other hematologic markers showed no significant effects on outcome. This study showed that the NLR may serve as a useful prognosticator for a high risk of multiple recurrences in patients with ACC.

MYB and MYBL1 in adenoid cystic carcinoma: diversity in the mode of genomic rearrangement and transcripts

AbstractMYB-NFIB and MYBL1-NFIB have been reported in ~60% of adenoid cystic carcinoma cases, but driver alterations in the remaining ~40% of adenoid cystic carcinoma remain unclear. We examined 100 adenoid cystic carcinoma cases for MYB and MYBL1 locus rearrangements by fluorescence in situ hybridization (FISH) with originally designed probe sets using formalin-fixed paraffin-embedded materials. Approximately one-third of samples were also analyzed by fusion transcript-specific RT-PCR and capture RNA sequencing. In the 27 cases with frozen materials, MYB-NFIB and MYBL1-NFIB fusion transcripts were detected in 9 (33%) and 6 cases (22%) by RT-PCR, respectively. Meanwhile, high expression of MYB (18 cases, 67%) or MYBL1 (9 cases, 33%) was detected in all 27 cases in a mutually exclusive manner, regardless of its form (full-length, truncation, or fusion transcript). Interestingly, genomic rearrangements around the corresponding highly-expressed gene were observed in all 27 cases by FISH, suggesting a causative relationship between genomic rearrangements and gene expression. Among the 100 cases, including additional 73 cases, 97 harbored genomic rearrangements in the MYB (73 cases) or MYBL1 locus (24 cases) including 10 cases with atypical FISH patterns undetectable through ordinary split FISH approaches: breakpoints far distant from MYB (5 cases) and a small NFIB locus insertion into the MYB (3 cases) or MYBL1 locus (2 cases). In clinicopathological analyses, histological grade, primary tumor size, and lymph node metastasis were identified as prognostic factors, whereas MYB/MYBL1 rearrangements were not, but were associated with histological grade. In the present study, MYB or MYBL1 locus rearrangement was detected in nearly all adenoid cystic carcinoma cases, and therefore it would be a good diagnostic marker for adenoid cystic carcinoma. However, fusion transcript-specific RT-PCR for MYB-NFIB and MYBL1-NFIB and ordinary split FISH assays for MYB and MYBL1 were less sensitive, and thus detection methods should be judiciously designed because of the diversity of rearrangement modes in adenoid cystic carcinoma.

Ataxia-Telangiectasia-Mutated Protein Expression as a Prognostic Marker in Adenoid Cystic Carcinoma of the Salivary Glands.

PurposeAdenoid cystic carcinoma (ACC) is a high-grade malignant tumor of the salivary glands, clinically characterized by multiple recurrences and late distant metastasis. Biological markers for assessing the prognosis of ACC have remained elusive. The purpose of this study was to investigate whether the protein expressions of ataxia telangiectasia mutated (ATM), p53, and ATM-mediated phosphorylated p53 are related to patient survival in ACC.Materials and MethodsIn this study, 48 surgical samples were used to assess the expressions of ATM and its downstream target p53. Fisher's exact test and Kaplan-Meier analysis were conducted to evaluate the role of ATM, p53, and phospho-p53 (S15) protein expressions in predicting patient survival and distant metastasis.ResultsMyb expression was positive in 85.4% of ACCs, but did not reflect patient survival rate. In contrast, low expression of ATM in cancer cells was significantly correlated with poor survival rate (p=0.037). Moreover, under positive p53 expression, low expression of ATM was highly predictive of poor survival in ACC (p=0.017).ConclusionThese data indicate that combined assessment of ATM and p53 expression can serve as a useful prognostic marker for assessing survival rate in patients with ACC of the salivary glands.

The unique luminal staining pattern of cytokeratin 5/6 in adenoid cystic carcinoma of the breast may aid in differentiating it from its mimickers.

Adenoid cystic carcinoma (AdCC) of the breast is an uncommon but distinct neoplasm composed of a dual cell population polarized around true glandular (luminal) spaces and pseudolumina. The aim of this study was to clarify whether various immunohistochemical markers (CK7, EMA, CD117, p63, calponin, CD10, S100, CK5/6, CK14, vimentin, and type IV collagen) can distinguish between the two cell types in classical AdCC (n=14) and in collagenous spherulosis (n=5). The sensitivity and specificity of these 11 markers to distinguish luminal from abluminal cells were evaluated using a curve created by plotting the true-positive rate (sensitivity) against the false-positive rate (1-specificity) at threshold settings of 0, 10, 50, and 70%. The most sensitive and specific markers for luminal cells in AdCC were CK7 and EMA; those for abluminal cells were type IV collagen, p63, and vimentin. CD10 and S100 did not act as abluminal markers in AdCC. CK5/6, one of the basal/myoepithelial markers, was expressed more frequently in luminal than in abluminal cells of AdCC. Thus, CK5/6 immunostaining resulted in a reverse expression pattern, analogous to what we recently documented in clear cells in mammary adenomyoepithelioma. In conclusion, compared with myoepithelial/abluminal cells of normal breast or collagenous spherulosis, the neoplastic abluminal cells of classical AdCC are characterized by enhanced vimentin and attenuated CD10 and S100. Furthermore, the luminal cells of AdCC show a unique aberrant staining pattern for CK5/6 that may aid in the differential diagnosis.

Fatty Acid Binding Protein 7 Is a Molecular Marker in Adenoid Cystic Carcinoma of the Salivary Glands: Implications for Clinical Significance

Adenoid cystic carcinoma (ACC) is an aggressive malignant neoplasm of the salivary glands. Its diagnosis is difficult due to overlapping features with other salivary tumors. Gene expression analysis may complement traditional diagnostic methods. We searched gene expression patterns in the Gene Expression Omnibus (GEO) database and in our tumor and normal samples. The biologic and prognostic potential of the identified genes was analyzed. The GEO data set of primary xenografted ACCs revealed that expression of five genes, engrailed homeobox 1 (EN1), fatty acid binding protein 7 (FABP7), hemoglobin epsilon 1, MYB, and versican (VCAN), was dramatically increased. mRNA expression of EN1, FABP7, MYB, and VCAN distinguished our sporadic ACCs from normal tissues and benign tumors. FABP7 expression appeared to be regulated differently from EN1 and MYB and was crossly correlated with poor prognosis in our ACC cohort. Immunohistochemistry showed that FABP7 protein was predominantly expressed in the nucleus of myoepithelial cells of both tubular and cribriform subtypes. In contrast, in the solid subtype, which is often associated with a lower survival rate, FABP7 protein was uniformly expressed in cancerous cells. One case with cribriform architecture and the highest level of FABP7 mRNA showed strong FABP7 staining in both duct-type epithelial and myoepithelial cells, suggesting that diffuse expression of FABP7 protein might be related to aggressive tumor behavior and poor prognosis. We propose FABP7 as a novel biomarker in ACC. The molecule may be useful in diagnosis and for identifying more effective therapies targeting this protein or upstream molecules that regulate it.

International collaborative validation of intraneural invasion as a prognostic marker in adenoid cystic carcinoma of the head and neck

The purpose of this study was to characterize the incidence, pattern of spread, and prognostic correlation of nerve invasion in patients with adenoid cystic carcinoma (ACC). Using 3 different pathological categories of perineural invasion, intraneural invasion, and perineural inflammation, we investigated the prognostic value of nerve invasion in a total of 495 ACCs from 9 international patient cohorts with median follow-up 90 months (range, 12-288 months). Of 239 patients (48%) with nerve invasion, 174 (73%) had perineural invasion, 65 (27%) intraneural invasion, and 37 (15%) perineural inflammation. Multivariate Cox regression analysis identified tumor site (p = .008; hazard ratio [HR] = 1.8; 95% confidence interval [CI] = 0.07-3.7) and intraneural invasion (p < .001; HR = 5.9; 95% CI = 0.8-12.3) as independent prognostic markers for both overall survival (OS) and disease-specific survival (DSS), but not of distant metastases. Although perineural invasion has no impact on survival, intraneural invasion is an independent predictor of poor prognosis. Recognition of intraneural invasion may help optimize treatment of patients with head and neck ACC.

International Collaborative Validation of Intraneural Invasion as a Prognostic Marker in Adenoid Cystic Carcinoma of the Head and Neck

International Collaborative Validation of Intraneural Invasion as a Prognostic Marker in Adenoid Cystic Carcinoma of the Head and Neck

Adenoid cystic carcinoma of the lacrimal gland: role of nuclear survivin (BIRC5) as a prognostic marker

This study aimed to evaluate the expression of nuclear survivin in adenoid cystic carcinoma (ACC) of the lacrimal gland and to determine if this expression is associated with histopathological features, markers of apoptosis and proliferation or clinical outcomes. Immunohistochemical staining for survivin, p53, Ki-67 and Bcl-2 was analyzed in 55 cases of ACC of lacrimal gland. Thirty-one cases (56.3%) expressed nuclear survivin. All cases expressed p53, Ki-67 and Bcl-2. Eleven cases (35.5%) had a high nuclear survivin score (NS-SCORE) and 20 cases (64.5%) had a low NS-SCORE. Cases with a high NS-SCORE had a shorter progression-free survival (PFS) (P < 0.0001), higher expression of Ki-67 (P < 0.005) and a solid tumour pattern >30% (P < 0.005). Nuclear expression of survivin impacts prognosis significantly and is thus a promising prognostic marker in ACC of the lacrimal gland.

Deletion of 1p32-p36 Is the Most Frequent Genetic Change and Poor Prognostic Marker in Adenoid Cystic Carcinoma of the Salivary Glands

Adenoid cystic carcinoma (ACC) is a relatively uncommon salivary gland malignancy known for its protean phenotypic features and pernicious clinical behavior. Currently, no effective therapy is available for patients with advanced nonresectable, recurrent, and/or metastatic disease. The purpose of this study is to identify prognostic factors other than tumor stage that can be used to predict the outcome of the patients with ACC. We used comparative genomic hybridization (CGH) to identify copy number aberrations in 53 primary ACCs. Array CGH and fluorescence in situ hybridization analysis was used to validate CGH results on selected cases. We correlated these copy number aberrations with clinicopathologic factors using Pearson's chi2 or by the two-tailed Fisher exact test. The disease-specific survival and disease-free intervals were generated by the Kaplan-Meier product limit method. Chromosomal losses (n = 134) were more frequent than gains (n = 74). The most frequent genetic change was the loss of 1p32-p36 in 44% of the cases followed by 6q23-q27, and 12q12-q14. The most frequently gained chromosomal regions were 8 and 18. Of the chromosomal aberrations, loss of 1p32-p36 was the only abnormality significantly associated with patient's outcome. This study, for the first time, identifies loss of 1p32-p36 as a significant aberration in ACC. Molecular characterization of 1p32-36 region using the available genomic technologies may lead to the identification of new genes critical to the development of novel therapeutic targets for this disease copy number aberration.

Hierarchical cluster analysis of myoepithelial/basal cell markers in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma

Distinguishing adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma of the salivary glands is important for their management. We studied the expression of several myoepithelial and basal/stem cell markers (smooth muscle actin, calponin, smooth muscle myosin heavy chain, metallothionein, maspin, and p63) by immunohistochemistry in 23 adenoid cystic carcinoma and 24 polymorphous low-grade adenocarcinoma, to identify the most useful marker or combination of markers that may help their diagnoses. The results were analyzed using hierarchical cluster analysis and χ2 test for trend. We noted diffuse expression of smooth muscle actin in 20 adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P<0.0001), calponin in 15 adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P<0.0001), smooth muscle myosin heavy chain in 15 adenoid cystic carcinoma vs one polymorphous low-grade adenocarcinoma (P=0.001), metallothionein in 22 adenoid cystic carcinoma vs eight polymorphous low-grade adenocarcinoma (P<0.001), maspin in 22 adenoid cystic carcinoma vs 14 polymorphous low-grade adenocarcinoma, and p63 in 21 adenoid cystic carcinoma vs 14 polymorphous low-grade adenocarcinoma. Hierarchical clustering of smooth muscle actin, calponin, smooth muscle myosin heavy chain, and metallothionein was virtually identical (κ≤0.0035), suggesting no significant advantage to their use in combination than individually. Diffuse smooth muscle actin expression showed the highest accuracy (91.5%) and positive predictive value (95.2%) for adenoid cystic carcinoma. Thus, diffuse expression of smooth muscle actin, calponin, smooth muscle myosin heavy chain, and metallothionein was highly predictive of adenoid cystic carcinoma, whereas maspin and p63 were frequently expressed in both tumors. In differentiating adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma, smooth muscle actin as a single ancillary test in support of the histological findings, appears to be as efficient as multiple immunohistochemical tests.

Loss of Maspin expression is a negative prognostic factor in common salivary gland tumors

Maspin, a 42kDa protein, belongs to the serine protease inhibitor (serpin) family and is suggested to have inhibitory effects on tumor-induced angiogenesis, tumor cell motility, invasion and metastasis and influences prognosis of tumor patients. The aim of the study was to analyze Maspin expression in salivary gland cancer as well as its prognostic impact on survival in comparison to clinical parameters. Immunohistochemical staining was carried out in 73 cases of salivary gland malignancies. High proportions of Maspin expression were observed in adenoid cystic carcinomas, mucoepidermoid carcinomas and carcinomas ex pleomorphic adenoma, low proportions were seen in salivary duct carcinomas. Acinic cell carcinomas did not show any Maspin expression. Analysis of the prognostic impact of Maspin expression was restricted to salivary gland carcinoma types of intermediate malignancy grade (adenoid cystic carcinoma, mucoepidermoid carcinoma and carcinoma ex pleomorphic adenoma). For these tumors, univariate analyses revealed that T-stage (p=0.025), age70 (p=0.0065), loss of Maspin (p=0.0016) and presence of residual tumor (p<0.001) correlated with poor prognosis. In multivariate analysis age70 (p=0.005) and loss of Maspin (p=0.036) were significant prognostic factors. Moreover, negative Maspin staining was associated with lymph node metastasis and residual tumor. According to these findings, Maspin might be useful as a new prognostic marker in adenoid cystic carcinoma and in salivary gland carcinomas with intermediate grade of malignancy where grading systems are still under debate.

Expression of KIT (CD117) in Neoplasms of the Head and Neck: An Ancillary Marker for Adenoid Cystic Carcinoma

Adenoid cystic carcinoma is an indolent salivary gland malignancy that is associated with a poor long-term prognosis. The distinction of adenoid cystic carcinoma from other head and neck neoplasms can occasionally be problematic, particularly in small biopsies. Recent studies suggest that KIT (CD117) might be useful as an ancillary marker for adenoid cystic carcinoma; however, the expression of KIT in other benign and malignant head and neck neoplasms, including those that might mimic adenoid cystic carcinoma, has not been well studied. Here we use two different antibodies against KIT to evaluate its expression in a series of 66 adenoid cystic carcinomas compared with its expression in 98 other neoplasms of the head and neck. Overall, 94% (n = 62) of adenoid cystic carcinomas from various anatomic sites and of various histologic subtypes were positive for at least one of the KIT antibodies, and 77% (n = 50) of adenoid cystic carcinoma cases were positive for both antibodies. This contrasted with only 8% (n = 8) of other head and neck neoplasms that were positive for both KIT antibodies (P < .001). It was of note that certain neoplasms, including pleomorphic adenoma, basal cell adenoma, polymorphous low-grade adenocarcinoma, and basal cell carcinoma, that can show histologic overlap with adenoid cystic carcinoma had significantly less KIT immunoreactivity than did adenoid cystic carcinoma (P < .001). In contrast, KIT expression did not reliably distinguish adenoid cystic carcinoma from basal cell adenocarcinoma and basaloid squamous carcinoma (P > .05). The overall sensitivity of the two KIT antibodies for adenoid cystic carcinoma was 82–89%, and the specificity was 87–88%. The findings in this study support the potential use of KIT immunoexpression for distinguishing adenoid cystic carcinoma from many other benign and malignant head and neck neoplasms.

Ki-67 as a prognostic marker in adenoid cystic carcinoma assessed with the monoclonal antibody MIB1 in paraffin sections.

The monoclonal antibody MIB1 recognizing the Ki-67 antigen in formalin-fixed, paraffin-embedded tissue was used to study the proliferative activity in 44 adenoid cystic carcinomas of the salivary glands. The antigen expression was compared with clinical factors, histopathological grading, and prognosis. The Ki-67 value was significantly higher in tumors from patients suffering from treatment failure than in nonfailures (P<0.001). The Ki-67 expression was also higher in tumors exhibiting areas more than 30% of the solid growth pattern and higher in sinonasal tumors than in other locations. By Cox regression analysis, Ki-67 more than 4% was the strongest prognostic indicator (P<0.005). Clinical stage and violation of surgical margins were also found to be independent significant prognostic indicators. We conclude that Ki-67 expression estimated by the use of MIB1 is a powerful tool for predicting the short-term prognosis for patients with adenoid cystic carcinoma.