Increased Ki-67 Labeling Index Research Articles

The Value of Ki-67 Labeling Index in Central Lymph Node Metastasis and Survival of Papillary Thyroid Carcinoma: Evidence From the Clinical and Molecular Analyses.

Recent evidence suggests that the Ki-67 labeling index is associated with lymph node metastasis and the prognosis of papillary thyroid carcinoma (PTC). We retrospectively evaluated the clinicopathological features of consecutive PTC patients between Jan 2019 and Oct 2020 in our medical center. The molecular analysis was also conducted by using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) program. The Chi-square test was performed for the comparison of variables between patients with central lymph node metastasis (CLNM) and not. Besides, univariate and stepwise multivariate logistic regression analyses were further used to determine the risk factors for CLNM in PTC. Our results showed that male gender (odd ratio (OR) = 3.02; 95% CI: 1.81-5.04), tumor size >1cm (OR = 2.81; 95% CI: 1.84-4.29), multifocality (OR = 2.08; 95% CI: 1.31-3.30, and Ki-67 labeling index (>3% and ≤5%: OR = 1.20; 95% CI: .73-1.97; >5%: OR = 3.85; 95% CI: 1.62-9.14) were independent risk factors for CLNM. After excluding the patients with harvested central lymph nodes <3, increased Ki-67 labeling index was still associated with the number of CLNM and the lymph node ratio. Additionally, the expression level of Ki-67 was significantly correlated with a higher N stage and worse disease-free survival in TCGA and validated GSE60542 datasets. Higher Ki-67 labeling index (>5%) is significantly associated with the CLNM in PTC patients, like other indicators of the male gender, larger tumor size, and multifocality. Besides, the Ki-67 was also determined to be associated with CLNM and DFS in PTC patients, which may act as an important molecular marker in PTC.

Clinicopathological investigation of secretory carcinoma cases including a successful treatment outcome using entrectinib for high-grade transformation: a case report

BackgroundSecretory carcinoma (SC) of the salivary gland is a recently described malignant tumor harboring characteristic ETV6-NTRK3 gene fusion. SC generally has a favorable clinical course, and is currently regarded as a low-grade carcinoma. However, a small subset of SCs demonstrates aggressive clinical features with histologically high-grade transformed morphology, the molecular pathogenesis of which has not yet been elucidated. In this study, we performed a clinicopathological and molecular genetic study of patients with SC of the head and neck displaying various clinical characteristics to investigate the differences of pathological and molecular genetics between low-grade and high-grade components of SC.Case presentationThree cases with SC of the head and neck, including a conventional low-grade SC and two high-grade transformed SCs are described. High-grade transformed SCs with histological features such as nuclear polymorphism, distinctive nucleoli and increased mitotic activity developed locoregional recurrence and distant metastasis. Immunohistochemical analysis revealed that low- and high-grade components showed different expression patterns for S-100 protein and mammaglobin, whereas all examined components were positive for p-STAT5. p53-positive cell population was markedly higher in one case with high-grade transformed SC. The proliferative activity of high-grade components was markedly increased, with the Ki-67 labeling index ranging up to 30–32%. A fluorescence in situ hybridization study with an ETV6 (12p13) break apart probe revealed split signals in the nuclei in all 3 cases. A targeted next-generation sequencing-based fusion assay demonstrated that all 6 clinical samples from the 3 patients showed the presence of the ETV6-NTRK3 fusion transcripts. One patient with high-grade transformed SC showed a dramatic clinical response to the pan-TRK inhibitor, entrectinib, for the treatment of locoregional recurrence and pulmonary metastasis.ConclusionsHigh-grade transformed SC showed aggressive clinical and pathological features with increased Ki-67 labeling index. Molecular genetic study of gene rearrangement appears to be beneficial treatment as the presence of ETV6-NTRK3 translocation may represent a therapeutic target in SC, particularly the high-grade transformed type.

Immune microenvironment in Barrett's esophagus adjacent to esophageal adenocarcinoma: possible influence of adjacent mucosa on cancer development and progression.

The immune microenvironment plays a pivotal role in cancer development and progression. Therefore, we studied the status of immune cells in esophageal adenocarcinoma (EAC) and adjacent Barrett's esophagus (BE) and their association with the clinical course of patients. We included 87 patients with EAC who underwent surgical resection or endoscopic submucosal dissection. CD3, CD8, Foxp3, p53, and Ki-67 were immunolocalized in EAC and adjacent BE (N = 87) and BE without EAC (N = 13). BE adjacent to EAC exhibited higher CD3+ lamina propria lymphocyte (LPL) numbers than BE without EAC. Abundant Foxp3+ LPLs in BE were associated with dysplasia and increased Ki-67 labeling index (LI) in BE glandular cells and tended to link to aberrant p53 expression. Abundant CD8+ LPLs in adjacent BE were associated with worse prognosis of EAC patients (P = 0.019). Results of our present study firstly revealed the potential influence of the tissue immune microenvironment of BE adjacent to EAC on cancer development and eventual clinical outcome of EAC patients. T cell infiltration could play pivotal roles in facilitating the dysplasia-adenocarcinoma sequence in BE. The number of Foxp3+ T cells is increased at the early stage of carcinogenesis and could help identify patients harboring dysplastic and highly proliferating cells. CD8+ T cells could reflect unfavorable inflammatory response in adjacent tissue microenvironment and help predict worse prognosis of EAC patients.

Precursor lesions of endometrial carcinoma

The 2014 WHO classification distinguishes between endometrial hyperplasia without atypia (EH) and atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN). AEH/EIN is characterized by crowded glands with cytologically atypical epithelium separated by little intervening stroma. Cellular atypia is characterized by nuclear enlargement and rounding, pleomorphism, loss of polarity, and presence of nucleoli. The diagnosis of atypia is facilitated by comparison with areas of adjacent normal and non-atypical glands, respectively. AEH/EIN is often associated with squamous but also secretory and mucinous metaplasia. Loss of PTEN and/or PAX2 immunoreactivity occurs in up to two thirds of AEH/EIN. In contrast, invasive low-grade endometrioid carcinoma shows confluent growth with loss of stroma and formation of labyrinth-like or cribriform structures. Differential diagnosis includes different forms of metaplasias, papillary proliferations, and hyperplastic polyps. Epithelial metaplasia may be present in various benign endometrial lesions as well as in endometrioid adenocarcinoma. AEH/EIN may also occur in endometrial polyps. Progestin therapy of AEH/EIN has low level of evidence but frequently leads to complete regression. Serous intraepithelial carcinoma (SEIC) is characterized by high-grade cellular atypia and polymorphism, detachment of cells, amutant immunoreactive pattern for the P53 and anincreased Ki67 labeling index. Although designated as precursor of serous carcinoma of the endometrium, biologically it is considered a non-invasive serous carcinoma since it may already be associated with massive extrauterine spread.

Expression of Ki-67 in odontogenic cysts: A comparative study between odontogenic keratocysts, radicular cysts and dentigerous cysts.

Introduction and Objectives:Odontogenic cysts are the most common cysts of the jaws and are formed from the remnants of the odontogenic apparatus. Among these odontogenic cysts, radicular cysts (RCs) (about 60% of all diagnosed jaw cysts), dentigerous cysts (DCs) (16.6% of all jaw cysts) and odontogenic keratocysts (OKCs) (11.2% of all developmental odontogenic cysts) are the most common. The behavior of any lesion is generally reflected by its growth potential. Growth potential is determined by measuring the cell proliferative activity. The cell proliferative activity is measured by various methods among which immunohistochemistry (IHC) is the commonly used technique. Most of the IHC studies on cell proliferation have been based on antibodies such as Ki-67 and proliferating cell nuclear antigen.Materials and Method:In the present study, the total sample size comprised of 45 cases of odontogenic cysts, with 15 cases each of OKC, RC and DC. Here, an attempt is made to study immunohistochemical (streptavidin-biotin detection system HRP-DAB) method to assess the expression of Ki-67 in different layers of the epithelial lining of OKCs, RCs and DCs.Observations and Results:Ki-67 positive cells were highest in epithelium of OKC as compared to DC and RC.Conclusion:The increased Ki-67 labeling index and its expression in suprabasal cell layers of epithelial lining in OKC and its correlation with suprabasal cell layers of epithelial lining in DC and RC could contribute toward its clinically aggressive behavior. OKC is of more significance to the oral pathologist and oral surgeon because of its specific histopathological features, high recurrence rate and aggressive behavior.

Screening for human urinary bladder carcinogens: two-year bioassay is unnecessary.

Screening for carcinogens in general, and for the urinary bladder specifically, traditionally involves a two-year bioassay in rodents, the results of which often do not have direct relevance to humans with respect to mode of action (MOA) and/or dose response. My proposal describes a multi-step short-term (90 day) screening process that characterizes known human urinary bladder carcinogens, and identifies those reported in rodent two-year bioassays. The initial step is screening for urothelial proliferation, by microscopy or by increased Ki-67 labeling index. If these are negative, the agent is not a urinary bladder carcinogen. If either of these is positive, an MOA and dose response analysis are performed. DNA reactivity is evaluated. If the chemical is non-DNA reactive, evaluation for cytotoxicity is performed. This involves examination of the urothelium and urine, the latter to identify the generation of urinary solids (e.g. calculi). If urinary solids are the cause of cytotoxicity, the MOA is not relevant to human cancer, but dose response becomes essential for evaluating potential toxicity to humans. If cytotoxicity occurs but no urinary solids are detected, urinary concentrations of the chemical and its metabolites are evaluated, and compared to in vitro cytotoxicity against rodent and human immortalized urothelial cell lines. Based on this process, a screen for urinary bladder carcinogenicity is reliable, and more importantly, can be based on MOA and dose response analyses useful in the overall risk assessment for possible human bladder cancer. The proposed procedure is shorter, less expensive and more relevant than the two-year bioassay.

Aberrant Akt Activation During Implantation Window in Infertile Women With Intramural Uterine Fibroids.

The objective of the study was to examine the expression and cellular distribution of key signaling components of the phosphatidylinositol-3-kinase (PI3K)/Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN)/Protein Kinase B (PKB/Akt) pathway during the window of implantation in infertile women with noncavity-distorting intramural uterine fibroids (n = 21) as compared to fertile controls (n = 15). Relative gene expression analysis of PIK3CA, PTEN, Akt1, and Akt2 genes in midluteal endometrial biopsies was performed by real-time polymerase chain reaction. Immunohistochemistry was used to evaluate the expression of PIK3CA, PTEN, phospho-PTEN, Akt1, Akt2, phospho-Akt1 (serine 473), phospho-Akt1 (threonine 308), and Ki67 proteins. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay was performed for apoptosis detection. In comparison to fertile controls, significant upregulation of Akt1 messenger RNA levels (2.16-fold; P < .05); cell-specific upregulation of the proteins phospho-PTEN ( P < .05), Akt1 ( P < .05), Akt2 ( P < .05), and p-Akt (S473; P < .001); and downregulation of PTEN ( P < .01) were observed in endometrium of infertile women with intramural fibroids. The ratio of p-PTEN/PTEN and p-Akt1 (S473)/Akt1 was also significantly higher in infertile women. Increased Ki67 labeling index in the glandular epithelium and significantly lower apoptotic index in glandular epithelium and stroma were seen in infertile women during the window of implantation. Aberrant Akt activation and the associated imbalance in endometrial proliferation and apoptosis observed in infertile women with intramural fibroids during the midsecretory phase might contribute to impaired endometrial receptivity leading to infertility in these patients.

Genomic Subtypes of Non-invasive Bladder Cancer with Distinct Metabolic Profile and Female Gender Bias in KDM6A Mutation Frequency

Bladder cancer incurs a higher lifetime treatment cost than other cancers due to frequent recurrence of non-invasive disease. Improved prognostic biomarkers and localized therapy are needed for this large patient group. We defined two major genomic subtypes of primary stage Ta tumors. One of these was characterized by loss of 9q including TSC1, increased KI67 labeling index, upregulated glycolysis, DNA repair, mTORC1 signaling, features of the unfolded protein response, and altered cholesterol homeostasis. Comparison with muscle-invasive bladder cancer mutation profiles revealed lower overall mutation rates and more frequent mutations in RHOB and chromatin modifier genes. More mutations in the histone lysine demethylase KDM6A were present in non-invasive tumors from females than males.

Mucin-poor and aggressive mucinous tubular and spindle cell carcinoma of the kidney: Two case reports.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare renal epithelial neoplasm. Although MTSCC is considered to be a low-grade and indolent neoplasm, aggressive cases have been recently reported. The present study discussed two additional cases of high-grade MTSCC causing multiple distant metastases with a fatal course. In case 1, a 71-year-old patient presented with hematuria and pyuria. Computed tomography (CT) scan of the right kidney revealed a mass lesion, for which partial nephrectomy was performed. However, a follow-up CT imaging revealed distant metastases in the liver, the paraaortic lymph nodes and the bone. Despite molecular targeted therapy and irradiation, the patient succumbed due to tumor progression. In case 2, a 64-year-old patient presented with an incidentally identified mass lesion in the right kidney. A laparoscopic nephrectomy was performed, and a follow-up CT imaging revealed metastases in the skin and lungs. The cytology of pleural effusion revealed pleuritis carcinomatosa. Histologically, both cases were diagnosed as mucin-poor MTSCC with high-grade transformation, which comprised uniform tumor cells primarily forming slender tubules. The tumors contained low- and high-grade regions. In addition, venous invasion and necrosis were observed. The tumor cells also demonstrated increased Ki-67 labeling indices and cellular tumor antigen p53 (p53) nuclear accumulation. High-grade transformation, large tumor size, necrosis, venous invasion, high Ki-67 labeling index and p53 nuclear accumulation are generally predictive findings for aggressive behavior of malignant tumors. In the current report, it was emphasized that MTSCC possesses a wide spectrum of clinicopathological features. Thus, careful postoperative investigation is required for MTSCC with high-grade elements due to its aggressive nature.

Myxoid and Sarcomatoid Variants of Adrenocortical Carcinoma: Analysis of Rare Variants in Single Tertiary Care Center.

The aim of this study is to describe rare variants of adrenocortical carcinoma (ACC) and to compare the prognosis with that of conventional ACC. We retrospectively reviewed 8 cases of myxoid variant, 1 sarcomatoid variant, and 14 cases of conventional ACC, who underwent surgical resection at the Asan Medical Center between 1996 and 2014. An analysis of the clinicopathological characteristics, including the Weiss score, Ki-67 labeling index, and reticulin framework assessment is presented. The mean age of patients with myxoid/sarcomatoid ACC was 45 years; 4 out of 9 patients were women. Mean primary tumor size was 12.9 cm and the mean weight was 702.4 g. Seven patients presented in an advanced stage (stage III/IV); 8 of these eventually developed distant metastasis. The mean Weiss score was 5.0 points and the Ki-67 labeling index was 15.6%. The extent of myxoid or sarcomatoid change on histological examination ranged from 10% to 75% of the examined tumor areas; reticulin framework alteration was observed in all cases. Four patients showed venous tumor thrombus. Most of the clinicopathological parameters were not significantly different from those of conventional ACC. However, myxoid or sarcomatoid variant (hazard ratios [HR], 3.59; 95% confidence intervals [CI], 1.13–11.38; P = 0.030) and Ki-67 labeling index (HR, 3.97; 95% CI, 1.18–13.41; P = 0.030) were independent predictors of overall survival after adjusting for age and sex. Myxoid or sarcomatoid histological features or an increased Ki-67 labeling index may be associated with poor overall survival in patients with ACC.

HOXC6 Overexpression Is Associated With Ki-67 Expression and Poor Survival in NPC Patients.

BACKGROUND: Homeobox (HOX) genes are expressed in adult cells and regulate expression of genes involved in cell proliferation as well as cell-cell and cell-extracellular matrix interactions. Dysregulation of HOX gene expression plays important roles in carcinogenesis in a variety of organs. Through data mining on a published transcriptome dataset, this study first identified Homeobox protein Hox-C6 (HOXC6) gene as one of the differentially upregulated genes in nasopharyngeal carcinoma (NPC). We aimed to evaluate HOXC6 expression and its prognostic effect in a large cohort of NPC patients.METHODS: We retrospectively examined the HOXC6 expression and Ki-67 index by immunohistochemistry in biopsy specimens from 124 patients with non-metastasized NPC. The results were correlated with the clinicopathological variables including disease-specific survival (DSS), metastasis-free survival (MeFS), and local recurrence-free survival (LRFS).RESULTS: HOXC6 high expression was positively correlated with increased Ki-67 labeling index, and significantly associated with increment of tumor stage (p=0.024), advanced nodal status (p<0.001) and American Joint Committee on Cancer (AJCC) stage (p=0.002). Its expression also correlated with worse prognosis in terms of DSS (p=0.008), MeFS (p=0.0047) univariately. In multivariate analyses, HOXC6 expression still remained prognostically independent to portend worse DSS (p=0.015, hazard ratio=1.988) and MeFS (p=0.036, hazard ratio=1.899), together with stage III-IV (p=0.024, DSS; p=0.043, MeFS).CONCLUSION: In summary, our results suggest HOXC6 may play a critical role in NPC progression and may serve as a potential prognostic biomarker in NPC patients.

Clinical and pathologic features of lung cancer expressing programmed cell death ligand 1 (PD-L1)

BackgroundProgrammed cell death 1 (PD-1) negatively regulates antigen receptor signaling upon binding by either of its ligands, programmed cell death ligand 1 or 2 (PD-L1/2). Blockade of this interaction with either PD-1 or PD-L1 antibodies has been successful in the treatment of human cancer, especially melanoma and non-small cell lung cancer. PD-L1 expression has been proposed as a predictor of tumor response. However, the relationships between PD-L1 expression and various clinicopathological characteristics remain unclear. Materials and methodsPD-L1 expression was examined in 220 non-small cell lung cancer specimens that were consecutively resected at our hospital after validating the E1L3N antibody immunohistochemical assay by comparing IHC and RT-PCR data for lung cancer cell lines. We evaluated the relationships between PD-L1 positivity, several clinical factors and the immunohistochemical expression of epithelial-mesenchymal transition (EMT), cancer stem cell and proliferative markers. ResultsPD-L1 was expressed in 22% of lung adenocarcinomas and 60% of squamous cell lung cancers. There was no significant association between PD-L1 expression and clinicopathological features in squamous cell lung cancer. However, in patients with lung adenocarcinoma, PD-L1 expression was significantly correlated with solid subtype histology, vimentin expression, increased Ki-67 labeling index and poor prognosis by multivariate analysis. ConclusionPD-L1 expression was associated with high proliferative activity and the EMT phenotype in adenocarcinoma but not in squamous cell carcinoma of the lung. PD-L1 expression was a significant poor prognostic factor in patients with lung adenocarcinoma.

Prognostic relevance of AIB1 (NCoA3) amplification and overexpression in breast cancer

AIB1 (amplified in breast cancer 1) is an estrogen receptorα (ERα) co-activator, known to be amplified and overexpressed in a fraction of breast cancers. It has been linked to prognosis and tamoxifen resistance. However, results have been ambiguous. The different functions of AIB1 in ERα-positive and -negative disease are poorly understood. Therefore, we analyzed the clinical significance of AIB1 in breast cancer with respect to ERα-status and characterized the subgroups. 2,197 breast carcinomas sampled on a pre-existing tissue microarray (TMA) were analyzed for AIB1 expression and amplification by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). AIB1 expression was detected in 60% of the tumors. It was associated with tumor size (p=0.003), high histological grade (p<0.0001), poor disease-specific, and overall survival (p=0.0018 and p=0.003). There was a strong inverse relationship between AIB1 and ERα expression (p<0.0001). AIB1 overexpression was associated with increased Ki67 labeling index (p<0.0001), even if analyzed for different ER expression levels. AIB1 amplification was found in 11% of the carcinomas. It was associated with high histological grade (p=0.0012), lymph node involvement (p=0.0163), and poor disease-specific survival (p=0.0032) but not with overall survival (p=0.1672) or ER status (p=0.4456). If ER-positive tumors were stratified according to their AIB1 amplification status, there was a significant worse disease-specific survival in cases showing AIB1 amplification (p=0.0017). AIB1 expression is associated with unfavorable prognosis and tumor phenotype. It seems to unfold its oncogenic potential at least in part independent from its role as an ERα co-activator. AIB1 has an impact on cell cycle regulation in ERα-positive as well as ERα-negative tumors. Furthermore, AIB1 amplification characterizes a subgroup of ERα-positive breast cancer with worse outcome. Therefore, AIB1 might be helpful to identify those ERα-positive breast cancers patients who are candidates for adjuvant chemotherapy.

Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum

Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ≤2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene.

Frequency of Ki-67 (MIB-1) and P53 expressions among patients with prostate cancer.

Prostate cancer is the most common malignant tumor in men. Tumor grade is one of the most important prognostic factors of prostate cancer. P53 and Ki-67 expressions have also been considered to be prognostic factors. This study was performed to investigate the frequency of these proteins expression and compare the obtained results with Gleason's grading. In this cross-sectional study, 49 paraffin blocks of prostate cancers were assessed. Tumor grade was determined according to the Gleason's criteria. Ki-67 and P53 expressions were determined by immunohistochemical staining. The obtained results were analyzed and evaluated using Spearman's statistical test (SPSS version 15). Three out of 49 (6.1%) cases were well differentiated, 21 (43%) moderately differentiated and 25 (51%) were poorly differentiated. P53 was negative in all well-differentiated cases. Ki-67 was negative in 14 cases (28%) including all well-differentiated tumors. Among moderately and poorly differentiated tumors Ki-67 was negative in eight (38%) and three (12%) of cases, respectively. A statistically significant relation was observed between the increased Ki-67 labeling index (LI) and increased Gleason's grade. Conversely, no statistically significant relation was found between P53 expression and increased Gleason's grade. According to the findings of this study, it seems that Ki-67 can be used as a prognostic factor for prostate cancer. On the other hand, the probable relation between P-53 and prostate cancer prognosis requires further studies.

An intracranial malignant solitary fibrous tumor

Intracranial malignant solitary fibrous tumor (SFT) is very rare. It was identified in a 39-year-old female patient who underwent malignant transformation over 6 months. MRI revealed an 8 × 5 × 6 cm mass with heterogenous strong enhancement in the left occipital lobe. Histologic findings and immunophenotype (positive for CD34, bcl-2 and vimentin, and negative for epithelial membrane antigen or S100 protein) of the primary tumor were typical of SFT. However, there was a focal area (<10% of tumor volume) showing hypercellularity, nuclear pleomorphism and increased Ki-67 labeling index (LI) of 10% (average, 1%). At the second operation, the recurrent tumor revealed full-blown histologic features of malignant SFT, such as infiltrative brain invasion, marked nuclear pleomorphism, frequent mitotic figures (15/10 high power fields), and high Ki-67 LI (25%). The presence of atypical histologic finding or increased Ki-67 LI in the typical SFT, although it is focal, needs to be mentioned in the diagnosis and also may require more aggressive surgical management.

Glomus Tumor of the Sinonasal Tract - Two Case Reports and a Review of Literature -

Herein we describe two cases of nasal glomus tumor. Histological findings were typical, save for one which was quite large (3.1 cm in its greatest dimension) with an invasive growth pattern and increased ki-67 labeling index (up to 10%). These features raised a red flag of similarity to a recently described “invasive glomus tumor of nasal cavity”, suggesting a more aggressive form of glomus tumor. However, objective criteria for this possibility is lacking at present and more similar case studies are needed to establish a truly aggressive form of glomus tumor.

KI-67 IN PITUITARY NEOPLASMS

KI-67, A MARKER of cellular proliferation, has been studied extensively in pituitary neoplasia. It is of relevance to various clinicopathological parameters, including tumor subtype, size, invasiveness, and recurrence, as well as patient age and sex. Generally, pituitary tumors behaving aggressively have increased Ki-67 labeling indices. Nonetheless, there is considerable overlap in Ki-67 labeling between noninvasive and invasive adenomas as well as between adenomas and pituitary carcinomas. Not only is there no general agreement regarding the relationship of Ki-67 labeling index and tumor invasiveness, but the same is also true of the association with pituitary tumor size, growth fraction, and recurrence. Whereas a number of studies found conclusive associations of Ki-67 labeling indices with aggressive behavior, size, and/or adenoma subtype, others fail to do so. It is evident that discrepant data regarding tumor behavior in part has its basis in nonuniform study criteria. For example, different investigators use varying criteria of tumor invasion and recurrence. Herein, we review the literature relating Ki-67 expression and various other clinicopathological parameters and conclude that uniform definitions and methods, as well as new markers, are key to improved treatment of pituitary tumors.

Subependymomas of the lateral ventricle: Tumor recurrence correlated with increased Ki-67 labeling index

Subependymomas of the lateral ventricles are rare tumors. We present two patients with subependymomas of the lateral ventricle, who underwent gross total resection of the tumor via transcallosal approach. The patient, with increased Ki-67 labeling index had recurrence of tumor two years after the initial operation. We emphasize at the risk of recurrence which is probably correlated with Ki-67 labeling index.

Ki-67 labeling index in breast carcinoma: An immunohistochemical study with correlation to molecular subtypes

22107 Background: Given the uncertain significance of Ki-67 labeling index (LI) in the published literature and new insight provided by expression profiling, we comprehensively examined 205 cases of consecutive breast carcinoma at our institution. Methods: The tumors were classified as follows: Luminal A (LUMA; ER score 200 or higher, HER2 negative), Triple Negative (TN; ER and PR H-score 10 or less, HER2 negative), ERBB2 (ER and PR H-score 10 or less, HER2 positive), Luminal A-HER2 Hybrid (LAHH; ER H-score 200 or higher, HER2 positive), Luminal Unclassified HER2 Positive (LUHP; ER H-score 11–199, HER2 positive), Luminal Unclassified HER2 Negative (LUHN; ER H-score 11–199, HER2 negative). Tissue microarrays (TMAs) were constructed. TMAs were stained with anti-Ki-67 antibody. Ki-67 LI was calculated using an image analysis system. Results: Of the 205 tumors, 113 (55%) were classified as LUMA, 32 (15%) as TN, 8 (4%) as ERBB2, 10 (5%) as LAHH, 34 (17%) as LUHN, and 8 (4%) as LUHP. Although some luminal A tumors showed increased Ki-67 LI (generally accompanied by high mitotic activity), the average Ki-67 LI was lowest in ductal-type LUMA (average LI of 15.8%) and other receptor positive and HER2 negative tumors. Ki-67 LI was highest for TN tumors with almost all tumors showing LI above 50%. The ERBB2 tumors showed an average LI of 27.8%. Ki-67 LI alone was sufficient in differentiating among LUMA, ERBB2 and TN molecular subclasses (p value <0.01). A higher Ki-67 LI predicted lymph node metastasis in non-triple negative tumors (p value = 0.018). Table shows the relationship between Ki-67 LI and lymph node status irrespective of tumor size and molecular classes. Conclusions: Ki- 67 LI is an important prognostic factor in breast carcinoma. There is correlation between Ki-67 LI and molecular classes; however, intra-class differences in proliferation activity of receptor positive tumors likely account for individual differences in prognosis and response to chemotherapeutic agents. Ki-67 LI and lymph node status (n = 171) LN Negative LN Positive Total LI: 1–10% 41 (71%) 17 (29%) 58 LI: 11–25% 36 (68%) 17 (32%) 53 LI: 26–50% 18 (49%) 19 (51%) 37 LI: 51% or more 19a (83%) 4 (17%) 23 a : Of these 19 cases, 14 were triple negative; LI: Labeling Index; LN: Lymph Node No significant financial relationships to disclose.