Ki-67 Proliferation Index Research Articles

Infantile rhabdomyofibrosarcoma with EGFR kinase domain duplication: a clinicopathological analysis of three cases

Objective: To investigate the clinicopathological and genetic features of infantile rhabdomyofibrosarcoma (IRFS) with EGFR kinase domain duplication (EGFR-KDD). Methods: The clinical, morphological and immunohistochemical features of three IRFS with EGFR-KDD diagnosed from January 2022 to January 2024 at Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed using PCR or next generation sequencing technique; and related literature was reviewed. Results: There were 1 male and 2 females, aged at presentation ranging from 1 to 4 years. The tumor occurred in the left thigh, right maxillofacial region, and right popliteal space. The presenting symptom was a painless mass which was accidentally discovered. The maximum diameter of tumors ranged from 3 to 5 cm. Microscopically, the tumors were poorly defined and composed of relatively monomorphic spindle cells, arranged in diffuse, fascicular growth patterns, with moderate pale eosinophilic cytoplasm. Mitoses were abundant. A few round rhabdomyoblastic tumor cells with abundant eosinophilic cytoplasm were found. There was no evidence of hemorrhage or necrosis. The tumor cells expressed vimentin, SMA, MSA, desmin, MyoD1 and myogenin; and the Ki-67 proliferation index was 10%-60%. RT-PCR showed EGFR-KDD in all three cases. Gene fusion was detected in three cases based on next generation sequencing, but only one case had EGFR-KDD. Follow-up data for 12 to 36 months showed two patients died of the disease and one patient was alive without recurrences and metastasis. Conclusions: IRFS is a rare soft tissue tumor that resembles infantile fibrosarcoma but has immunohistochemical evidence of rhabdomyoblastic differentiation. It more commonly occurs in infants and tends to appear in limbs and torso with poor prognosis. Aggressive multimodality treatment is recommended for these patients. EGFR-KDD may be a genetic driver to IRFS. Clinical response to EGFR targeted therapy might be promising in the future.

Gastrointestinal hamartomatous inverted hyperplastic polyps: a clinicopathological analysis of ten cases

Objective: To investigate the clinicopathological features, diagnosis, genetic alterations, and biological behaviors of hamartomatous inverted hyperplastic polyp (HIHP) in the gastrointestinal tract. Methods: The clinical, sonographic, endoscopic and pathologic data of 10 HIHP cases diagnosed at the First Affiliated Hospital of Air Force Medical University, Xi'an, China from January 2013 to March 2024 were collected. Their clinicopathological features and histological morphology were analyzed. The cases were further divided into 3 histologic subtypes. Follow-up information was collected to analyze the relationship between histological subtype and prognosis. Results: There were 5 males and 5 females in this cohort. The age of onset was 45-68 years, with a median age of 60.5 years. The polyp-involved sites included 2 cases in gastric fundus, 6 cases in gastric body, 1 case in gastric antrum, and 1 case in duodenum. Digestive endoscopy showed mucosal protrusion lesions in all cases, except 1 case (case 10) of shallow depression on the surface, with the maximum diameter ranging 0.5-2.5 cm. Endoscopic ultrasonography showed multilocular cystic low-density shadows, with septal enhancement (case 4). The preoperative clinical diagnosis was gastric polyp, ectopic pancreas or gastrointestinal stromal tumor. Two cases showed type 1 morphology (i.e., connected with the mucosa, with clear smooth muscle boundaries). One of them (case 10) had a clear opening to form a vase-like morphology, while the other (case 4) had no obvious opening with the surface mucosa. Three cases showed type 2 morphology (i.e., not connected with the mucosa, with clear smooth muscle boundaries). Five cases showed type 3 morphology (i.e., not connected with the mucosa, without clear smooth muscle boundaries or hyperplastic smooth muscle that separated hyperplastic glands showing lobular configuration). Among them, one case of duodenal lesions (case 9) showed gastric type gland hyperplasia and expansion, including gastric fossa, gastric fundic gland and pyloric gland, with various arrangement and combination, accompanied by smooth muscle hyperplasia. In case 10, there was leiomyomatous proliferation in the stroma. The cases 2 and 4 had atypical glandular structures and cell morphology, but immunohistochemistry showed wild-type expression pattern of p53 and a Ki-67 proliferation index of less than 1%, suggesting that it was reactive atypia secondary to inflammation. The results showed that 3 cases had different gene mutations, and no recurrent gene change was identified. All patients survived without disease during the follow-up period of 1-130 months. Conclusions: HIHP is a benign lesion and has no consistently detectable genetic alterations. The histological characteristics of gastrointestinal polyps are complex. Especially, the types 1 and 3 of HIHP have unique gross and microscopic features, which require combination of proper endoscopic sampling and histological examination to correctly classify them.

Sclerosing Odontogenic Carcinoma: A Unique Odontogenic Carcinoma with Metastatic Potential.

The recent World Health Organization (WHO) classification of odontogenic tumours defines Sclerosing Odontogenic Carcinoma (SOC) as a rare primary intraosseous carcinoma (PIOC) of the jaws. With the exception of one case, there have been no cases of SOC with metastatic disease. We report a unique case of SOC with neck node metastases, further expanding the clinical, radiological and histological spectrum of this rare intriguing tumour. A 52-year-old female presented with a destructive radiolucent lesion of right mandible. Incisional biopsy was interpreted as desmoplastic ameloblastoma. The segmental mandibulectomy specimen was histologically consistent with SOC with positive anterior margin. Further resection with neck dissection revealed positive right levels IB and IIA nodes. Immunohistochemistry and Fluroscent In Situ Hybridization (FISH) were performed to confirm the diagnosis. The tumour was positive for CK5, p63, p40 and negative for CK19, CK20, CK7, SOX-10, S100, ER, PR, BRAFV600E, and EWSR1 gene rearrangements. Ki67 was 15%. To avoid confusion with PIOC, a high grade squamous cell carcinoma of the jaws with poor prognosis, SOC may be best defined as a rare infiltrative and locally aggressive odontogenic carcinoma with metastatic potential but with a reasonably favourable outcome. SOC shares similar histologic features with many benign and malignant tumours. An appropriate panel of immunohistochemical markers, in conjunction with special stains and molecular studies can help refine the differential diagnosis. It appears that a Ki67 proliferation index of more than 10%, may pose a risk for nodal metastasis and may assist in planning the clinical management. To achieve lower rates of positive margins and tumour recurrence, a wider resection margin (more than a centimetre) is recommended.

Clinicopathologic Features and Viral Status of Low-risk HPV6 and HPV11-Associated Squamous Cell Carcinoma of the Uterine Cervix and Vulva.

Despite being designated as "noncarcinogenic" human papillomavirus (HPV) types, mono-infection with HPV6 or HPV11 has been found in squamous cell carcinomas (SCCs) at specific sites, including the larynx, penis, anus, and rarely, the lower female genital tract. The association between clinicopathologic features, viral status, and the carcinogenic mechanisms related to these low-risk HPVs remains unclear. The current study characterizes a series of low-risk HPV6 and HPV11-associated SCCs of the uterine cervix (6 cases) and vulva (2 cases). The diagnosis of SCC was made through the identification of stromal invasion in 6 cases. In case 2, the diagnosis of cancer was made after metastases to the sigmoid colon and liver. The patient in case 6 was diagnosed with intramucosal papillary SCC given multiple recurrences. While all tumors displayed a similar verruco-papillary architecture, the cytologic features, and immunostaining patterns suggest 2 groups of lesions: one with high-grade cytology and a high Ki-67 proliferation index (>60% of lesional cells), and the other with low-grade cytology and a low Ki-67 (20% to 30% of lesional cells). The detection of HPV6 in 7 of 8 cases underscores its critical role in carcinogenesis at these anatomic sites. Case 8 represented the only patient who was infected with HPV11 and who had a well-controlled human immunodeficiency virus infection. Correlating with viral status, all cases, except case 7, demonstrated a negative or focal p16 staining pattern. In case 7, despite a block pattern of p16 staining often seen in predicting high-risk HPV, we employed several methods to confirm HPV6 as the sole HPV infection. Although this descriptive study does not establish an etiological mechanism for how HPV6/11 leads to malignant transformation, our results exclude the possibility of viral integration through a quantitative polymerase chain reaction-based analysis of the E2/E6 ratio. Our study highlights and expands upon the clinicopathologic features of a distinct group of low-risk HPV6/11-associated SCCs in the cervix and vulva. Although rare, recognizing this group of lesions is important for pathologists and oncologists, as it provides a basis for guiding appropriate prevention strategies and treatment modalities based on the viral type.

Investigating the Role of DNA Ploidy and Proliferation Index in Distinguishing Ameloblastoma from Ameloblastic Carcinoma.

This study aimed to investigate the role of DNA ploidy and proliferation index in distinguishing ameloblastoma (AB) from ameloblastic carcinoma (AC). The study included 29 ACs, 6 conventional ABs that transformed into ACs, and a control cohort of 20 conventional ABs. The demographics and clinicopathologic details of the included cases were summarised and compared. The Ki-67 proliferation index was scored using the QuPath open-source software platform. DNA ploidy analysis was performed using high-resolution flow cytometry. The cohort of ABs presented at an overall younger age compared to both primary and secondary ACs. There was a statistically significant difference between the median duration of the tumour when comparing primary and secondary ACs, with ACs presenting with longer durations than the AB cohort. All cases of AC showed a relatively high median proliferation index of 41.7%, with statistically significant higher scores compared to ABs. DNA ploidy analysis showed that all cases in the AB cohort were diploid. Two diploid cases of AB that transformed into ACs were aneuploid when the corresponding secondary AC was analysed. Fourteen cases of AC were diploid and 12 were aneuploid, with no statistically significant association found between DNA ploidy status of primary and secondary ACs. A statistically significant difference was noted when the DNA ploidy status of ABs was compared to that of ACs. When comparing the Ki-67 proliferation score of ACs to their DNA ploidy status, no statistically significant association was noted. DNA ploidy analysis and proliferation index via Ki-67 IHC are useful ancillary tests that may be used to support a diagnosis of AC and may assist in distinguishing between challenging cases of AB and AC.

High Ki67 expression, HER2 overexpression, and low progesterone receptor levels in high-grade DCIS: significant associations with clinical practice implications

Simple summaryWe investigated the role of Ki67, a ubiquitous marker in cancer, within the context of ductal carcinoma in situ (DCIS), a precursor of invasive breast cancer. Through rigorous analysis of histopathological and immunopathological samples from a substantial cohort, this study revealed robust correlations between heightened Ki67 expression, diminished progesterone (PR) levels, and HER2 overexpression, indicative of aggressive DCIS phenotypes. These findings offer novel insights into the surrogate immunomolecular subtyping landscape of DCIS, potentially refining risk stratification and therapeutic approaches. This elucidation underscores the translational significance of Ki67 as a prognostic and predictive biomarker in DCIS, with implications for personalized treatment paradigms and patient outcomes.BackgroundThe Ki67 proliferation index is widely used in various tumors, including invasive breast carcinoma (IBC). However, its prognostic utility is often constrained by technical complexity. Its diagnostic and clinical significance in ductal carcinoma in situ (DCIS) remains uncertain. We studied Ki67 immunohistochemistry interobserver diagnostic agreement at different cutoff values in high-grade DCIS. Additionally, we investigated the associations between Ki67 expression, PR levels, and human epidermal growth factor receptor 2 (HER2) in high-grade DCIS among various subtypes (Luminal (Lum) A, LumB HER2-, LumB HER2+, HER2-enriched, and triple-negative)).MethodsUsing histopathological specimens from 484 patients diagnosed with DCIS between 1996 and 2018, we implemented the 2013 St. Gallen recommendations for surrogate immunomolecular subtyping of IBC. Subtypes were classified, and the Ki67 interobserver diagnostic agreement between Counting Pathologist 1 (CP1) and CP2 was calculated using Cohen’s kappa coefficient at various cutoff values.ResultsThe Cohen’s kappa coefficient for interobserver agreement between CP1 and CP2 was κ = 0.586, indicating moderate agreement. Ki67 levels varied significantly among subtypes (p < 0.0001), with a median Ki67% being higher in cases with invasive components (p = 0.0351). Low PR combined with high Ki67% was significantly associated with HER2 overexpression (p = 0.0107).ConclusionsInterobserver agreement for the Ki67 count was moderate. Ki67 expression showed considerable variability in high-grade DCIS. Low PR levels combined with high Ki67 expression were linked to HER2 overexpression, showing possible clinical implications for identifying high-risk DCIS.

P-52 ASYMPTOMATIC MIXED PITUITARY MACROADENOMA IN A YOUNG MALE PATIENT

Abstract Introduction Central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, representing 0.5-1.0% of all pituitary adenomas. The etiopathogenesis of TSH-secreting-adenomas is unknown and no definite role for various oncogenes has been proven. Plurihormonal pituitary adenomas reveal greater tumor recurrence and local invasion than do mono-secreting pituitary adenomas and therefore they need to be followed more closely. Clinical Case We present the case of a 19-year-old male who was admitted to the endocrinology clinic, was asymptomatic, and had abnormal thyroid tests during routine examinations. Laboratory tests revealed TSH 1.33 (normal RI), freeT4 2.5 (high), freeT3 6.78 (high), and the patient had tachycardia (pulse 120/min) on physical examination, but had no complaints. Thyroid antibody tests were negative, and ultrasonography revealed normal thyroid gland size and homogeneous parenchyma. Alpha subunit test was requested with suspicion of TSHoma and genetic test was requested considering thyroid hormone receptor resistance. In the pituitary panel tests, the patient's GH and IGF1 tests were found to be high for his age and gender, The lowest GH value in the GH-OGTT test was 3.95 ng/mL. LH was high but testosterone was within the normal reference range. The patient was found to have mandibular prognathism and his secondary sex characteristics were normal. Pituitary MRI revealed a nodular appearance on the left side of the pituitary gland, measuring 13x9 mm, hypointense on T1A, hyperintense on T2A, and showing contrast medium uptake. The infundibulum deviates to the right, and there is no pressure on the optic chiasm. Visual field test was normal. AlphaSubunit pituitary tumor marker value was found to be high at 1.9ng/mL (RIs ≤0.5). The genetic test for resistance to thyroid hormone, also came back normal. The patient underwent endoscopic transsphenoidal pituitary adenomectomy due to pituitary macroadenoma by an experienced neurosurgeon. No postoperative complications developed. In cytopathological evaluation, histochemical studies performed with silver stain showed that the reticulin roof was lost. In immunohistochemical studies, SF-1, PIT-1, LH (diffuse), GH (densely granular), TSH (rare) and LMWK (perinuclear cytoplasmic weighted) were positive. T-PIT and Prolactin were negative. Ki-67 proliferation index was 5%. Postoperative pituitary tests were normal and no deficiency was observed and no treatment was required. At the postoperative 3rd month follow-up, the lowest GH value in the GH-OGTT test was 0.16 ng/mL, and no residual mass was observed in the pituitary MRI. The patient, who had no postoperative complaints, is being followed up by the endocrinology clinic. Conclusion Mixed pituitary tumors are rare and can sometimes appear as silent tumors, but may be aggressive during follow-up, so better follow-up is necessary.Table 1:Pituitary panel biochemical results

Low-Grade Myofibroblastic Sarcoma in the Oral Cavity: Case Report and Clinical Insights

Background/Objectives: Low-grade myofibroblastic sarcoma is a rare malignant myofibroblastic tumor, first described by Gabbiani et al. in 1971. It predominantly affects adult males and is uncommon in children. The tumor can occur anywhere in the body, with a preference for the limbs and head and neck regions, including the oral cavity. Methods: A case report of a 22-year-old male patient with no systemic conditions who presented with a painless, red, firm swelling between teeth 34 and 35 was examined. Panoramic radiography was unremarkable. The lesion measured 19 × 8 mm. Histological analysis revealed a spindle cell proliferation with atypia. Immunohistochemical staining was positive for SMA and showed a low Ki-67 proliferative index, while negative for Desmin, CD34, and beta-catenin. The final diagnosis was low-grade myofibroblastic sarcoma. Results: After surgical excision, the lesion recurred within one month. The patient was referred to the Portuguese Institute of Oncology for further treatment. Conclusions: Low-grade myofibroblastic sarcoma is a rare tumor with a tendency for local recurrence and metastasis. Accurate diagnosis, which includes histological examination and immunohistochemistry, is essential to differentiate it from other benign and malignant lesions. This case highlights the importance of an incisional biopsy to confirm diagnosis prior to surgical excision, thereby reducing the risk of relapse and enabling appropriate treatment planning.

Dynamic contrast enhanced MRI in nodal lymphoma: correlation of quantitative MR perfusion parameters with lymphoma subtype, Lugano stage and Ki-67 index.

Research into the intratumoral microenvironment in lymphoma has been escalated along with improved survival and new targeted therapies with an intent to refine risk stratification and prognostication. Various studies have reported significance of quantitative DCE-MRI parameters for predicting biological behaviour of various tumors. This study is an endeavour to supplement the existing literature on quantitative DCE-MRI in nodal lymphoma. To study the correlation of quantitative DCE-MRI parameters of Ktrans, Kep and Ve with subtype, Lugano stage at diagnosis and Ki-67 proliferation index (PI) in nodal lymphoma. 33 patients of age > 12 years with newly diagnosed nodal lymphoma underwent DCE-MRI. Ktrans, Kep and Ve were generated from extended Tofts model and correlated with lymphoma subtype, Lugano staging and Ki-67 PI. Mean Ktrans and Kep values were significantly higher in non-Hodgkin's lymphoma (NHL) than in Hodgkin's lymphoma (HL). Considering Ki-67 PI value of > 45% as aggressive lymphoma, the mean Ktrans (659.37 x 10-3min-1 versus 288.00 x 10-3min-1, p < 0.001) and Kep (1256.63 x 10-3min-1 versus 689.82 x 10-3min-1, p = 0.004) values in aggressive lymphomas were significantly higher compared to non-aggressive lymphomas. ROC curve analysis revealed a threshold Ktrans value of ≥ 359 x 10-3min-1 and Kep value of ≥ 853 x10-3 min-1 for diagnosing aggressive lymphomas with a sensitivity of 95%, 90%, specificity of 100%,82% and diagnostic accuracy of 91.7%,86.7% respectively. There was no significant difference in DCE-MRI parameters of various Lugano stage subgroups. DCE-MRI parameters have the potential to non-invasively predict the subtype, aggression and Ki-67 PI in nodal lymphoma. The knowledge that Ktrans is higher in aggressive lymphomas is novel. It adds to previous literature regarding MR perfusion in various neoplasms.

Correlation on metabolic complete response on positron emission tomography and pathological complete response in patients with breast cancer after neoadjuvant chemotherapy.

The use of neoadjuvant chemotherapy in treating breast cancer has expanded in recent years. There was increased interest in using positron emission tomography (PET) for the evaluation of treatment response. We aimed to study the accuracy of metabolic complete response (mCR) on PET scan in predicting pathological complete response (pCR) after neoadjuvant treatment. Between January 1, 2014 and June 30, 2019, 356 consecutive patients who completed neoadjuvant treatment underwent PET scan before surgery. 207 patients (58.1%) achieved mCR and 128 patients (36.0%) achieved pathologic CR. Among mCR patients, 101 (48.8%) had pCR. Among pCR patients, 27 (21%) did not achieve mCR on PET. The overall sensitivity of predicting pCR with mCR was 78.9% and specificity of 53.5%. The overall accuracy was 0.691 by area under the receiver operating characteristic curve (AUC). Analysis using mCR to predict breast/axilla pCR had a sensitivity of 76.2%/67.9%, specificity of 54%/62.1%, and AUC of 0.682/0.675, respectively. Sensitivity and specificity were highest among HR-/HER2+ (87.1% and 57.1%), followed by HR+/HER2- (85% and 59.6%) and triple negative (82.1% and 54.1%) and the lowest were HR+/HER2+ (triple positive) (69.4% and 40.3%). There was little difference in sensitivity and specificity among the high and low Ki67 proliferation index (78.3% vs. 75% and 52.1% vs. 62.5%). PET was useful in evaluation of tumor response to neoadjuvant chemotherapy especially in the HR-HER2+ subtype. However, its accuracy was not high enough to replace surgery.

Neoadjuvant chemotherapy and pathological complete response in hormone-positive HER2-negative breast cancer: influence of progesterone receptor expression, tumor grade and Ki-67

Aim. To study the role of progesterone receptor expression, tumor grade and Ki-67 level as possible predictors of pathological complete response (pCR) to neoadjuvant chemotherapy in patients with stage IIA–IIB (cT1–2N1, cT2–3N0M0) breast cancer of hormone-positive HER2-negative subtype.Materials and methods. We retrospectively analysed the efficacy of neoadjuvant chemotherapy (4AC+12P/4T) in 100 patients with cancer stages IIA–IIB (cT1–2N1, cT2–3N0M0) of hormone-positive HER2-negative subtype treated at the P.A. Hertsen Moscow Oncology Research Institute from 2013 to 2022. The pathological response to neoadjuvant chemotherapy depending on the level of progesterone receptor expression, tumour grade (G) and tumour proliferation index (Ki-67) were evaluated.Results. Pathological complete response was achieved in 12 of 100 patients. The progesterone receptor expression ≤3 Allred pCR scores were found in 16.1 % (5/31) of patients, whereas with progesterone receptor &gt;3 scores in 10.1 % (7/69) (odds ratio 1.703; 95 % confidence interval (CI) 0.495–5.860; p = 0.507). Patients with high tumour grade (G3) achieved pCR in 12.1 % (4/33) cases and with G2 – in 11.9 % (8/67) (odds ratio 1.017; 95 % CI 0.283–3.658; p = 1.000). With the Ki-67 levels ≥50 % pCR was achieved in 14.6 % (7/48) cases compared to 9.6 % (5/52) with Ki-67 levels &lt;50 %(odds ratio 1.605; 95 % CI 0.473–5.445; p = 0.544). The Ki-67 threshold for achieving pCR was 70 % (area under the ROC curve 0.663 ± 0.090; 95 % CI 0.486–0.840; p = 0.068) and for progesterone receptors was 3 points (area under the ROC curve 0.625 ± 0.080; 95 % CI 0.467–0.782; p = 0.156).Conclusion. This analysis highlights the importance of considering all clinical and morphological characteristics of the tumour when planning the scope of treatment for hormone-positive HER2-negative breast cancer. The results obtained may serve as a basis for a more personalised therapeutic approach.

Fluorescence Lifetime Imaging of NAD(P)H in Patients' Lymphocytes: Evaluation of Efficacy of Immunotherapy.

The wide variability in clinical responses to anti-tumor immunotherapy drives the search for personalized strategies. One of the promising approaches is drug screening using patient-derived models composed of tumor and immune cells. In this regard, the selection of an appropriate in vitro model and the choice of cellular response assay are critical for reliable predictions. Fluorescence lifetime imaging microscopy (FLIM) is a powerful, non-destructive tool that enables direct monitoring of cellular metabolism on a label-free basis with a potential to resolve metabolic rearrangements in immune cells associated with their reactivity. The aim of the study was to develop a patient-derived glioma explant model enriched by autologous peripheral lymphocytes and explore FLIM of the redox-cofactor NAD(P)H in living lymphocytes to measure the responses of the model to immune checkpoint inhibitors. The light microscopy, FLIM of NAD(P)H and flow cytometry were used. The results demonstrate that the responsive models displayed a significant increase in the free NAD(P)H fraction α1 after treatment, associated with a shift towards glycolysis due to lymphocyte activation. The non-responsive models exhibited no alterations or a decrease in the NAD(P)H α1 after treatment. The FLIM data correlated well with the standard assays of immunotherapy drug response in vitro, including morphological changes, the T-cells activation marker CD69, and the tumor cell proliferation index Ki67. The proposed platform that includes tumor explants co-cultured with lymphocytes and the NAD(P)H FLIM assay represents a promising solution for the patient-specific immunotherapeutic drug screening.

The importance of Ki-67 proliferation index in small cell lung cancer

BackgroundAs in numerous cancers, the connection between the Ki-67 proliferation index and response to treatment in cellular breakdown in the lungs is underlined. The purpose of this study was to investigate the connection between the Ki-67 proliferation index and radiotherapy’s therapeutic and survival effects in small cell lung cancer.MethodsThe limited-stage small cell lung cancer patients in our hospital were retrospectively reviewed. Patients receiving standard chemoradiotherapy were included in the study. Age, sex, cancer stage, comorbidities, response to treatment, and survival time were recorded. Bronchoscopic or transthoracic lung biopsy specimens which were taken at the time of diagnosis were stained with the Ki-67 immunohistochemical stain. Survival of patients and treatment response were compared statistically with the Ki-67 values.ResultsThe Ki-67 proliferation index (62.29 ± 7.52) was lower in patients with partial response than in patients with complete response (77.08 ± 2.84) (p < 0.001). When the correlation between survival time and Ki-67 was examined, there was a positive correlation between the Ki-67 and survival time (p: 0.019; r: 0.426). The patients were divided into two groups: Ki-67 < 68.70 and Ki-67 ≥ 68.70. In patients with Ki-67 ≥ 68.70, the survival rate was better than that of patients with Ki-67 < 68.70 (p: 0.012). In Cox regression analysis, Ki-67 PI < 68.7 was found that increased mortality by 2742 times independently.ConclusionsPatients with a high Ki-67 had a better survival effect than those with low Ki-67, and patients with complete responses had a higher Ki-67 value.

Ketogenic diet with oxyresveratrol and zinc inhibits glioblastoma and restores memory function and motor coordination.

To date, there is no effective cure for the highly malignant brain tumor glioblastoma (GBM). GBM is the most common, aggressive central nervous system tumor (CNS). It commonly originates in glial cells such as microglia, oligodendroglia, astrocytes, or subpopulations of cancer stem cells (CSCs). Glucose plays an important role in the, which energy metabolism of normal and cancer cells, but cancer cells exhibit an increased demand for glucose is required for their differentiation and proliferation. The main aim of this study is to explore the anti-cancer efficacy of the ketogenic diet against GBM. Also, this research focuses on the identification of the catalytic action of zinc in epigenetic modulators such as oxyresveratrol and ensures the combinatorial effect in the treatment of GBM. In this study, we have evaluated various parameters to understand the therapeutic efficacy of the treatment groups through in vivo experiments against aggressive brain tumors. Intracerebroventricular experiments were performed to induce the tumor in the animals and estimate the tumor burden and proliferative index. Followed by the Morris water maze, an open field test, and rota rod was performed to evaluate the memory and motor coordination. To understand the glucose, and ketone level modification before and after treatment, the level of glucose and ketone was analyzed. Moreover, the zinc level is assessed using flame atomic absorption spectroscopy. The results suggested that the ketogenic diet has an anti-cancer efficacy against C6-induced GBM cell lines. Also, it exerts a synergistic effect with the epigenetic modulator, oxyresveratrol, and zinc against GBM cell lines. Moreover, the treatment groups improved memory and motor coordination and modified the glucose and ketone levels to reduce the tumor burden and Ki-67 proliferative index. This study revealed the therapeutic effect of the ketogenic diet along with its combination such as oxyresveratrol and zinc against the C6-induced GBM in the Wistar rats. Also, it improved memory and motor coordination and reduced tumor growth. It also modified the glucose and ketone levels in the tumor-induced animal and supported to diminish the tumor burden.

Evaluation of HER2-Low breast carcinoma in metastatic settings: a cytological approach to proliferation and survival.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer, defined by HER2 immunohistochemistry scores of 1+ or 2+ without gene amplification, represents a unique subgroup with emerging therapeutic implications. Limited data describe the behavior of HER2-low tumors, particularly in metastatic settings. This study evaluated the frequency of HER2-low expression, Ki-67 proliferation index, and survival outcomes across HER2 subtypes in metastatic breast carcinoma using cytology specimens. A 3-year retrospective analysis identified 43 patients with metastatic breast carcinoma diagnosed via fine-needle aspiration or exfoliative cytology. HER2, ER, PR, and Ki-67 status were determined by immunohistochemistry, with equivocal HER2 cases assessed by in situ hybridization. Survival outcomes were estimated using the Kaplan-Meier method, with Cox regression identifying predictors of survival. Among 43 cases, 31 (70.5%) were HER2-low, 6 (13.6%) HER2-positive, and 6 (13.6%) HER2-zero. HER2 discordance between primary and metastatic lesions occurred in 19%, mainly involving transitions to HER2-low status. Hormone receptor positivity was more frequent in HER2-low tumors (71%) than HER2-zero tumors (33%) (P<0.001). Mean Ki-67 was highest in HER2-low (45%) versus HER2-negative (34%) and HER2-positive (33%) cases (P=0.549). Median survival was 13 months for HER2-low and 5 months for HER2-negative patients; survival differences were not significant (P=0.225). Younger age (HR=0.240, P=0.048) and hormone receptor positivity (HR=0.273, P=0.011) were significant predictors of survival. HER2-low expression is prevalent in metastatic breast carcinoma with a unique hormone receptor profile. Findings highlight the need for reassessment of HER2 status in metastatic settings, with potential therapeutic implications.

Acanthomatous ameloblastoma with mucinous glandular differentiation in a dog

This report describes an atypical case of canine acanthomatous ameloblastoma (CAA) with mucinous glandular differentiation in a 12-year-old male Chihuahua with a right mandibular mass. Initially diagnosed as CAA by biopsy, computed tomography revealed bone lysis, prompting surgical excision. Histological examination showed lobular growth with two distinct neoplastic cell populations: typical CAA-like cells and a minor glandular structure population. Mucinous glandular differentiation in CAA is undocumented in veterinary literature. Immunohistochemistry showed positivity for cytokeratin AE1/AE3 in all tumor cells, and cytokeratin CAM5.2 and Alcian blue staining confirmed glandular cells and mucin. A low mitotic and K-i67 proliferation index suggested low-grade malignancy. This rare case highlights the need for comprehensive histopathological and immunohistochemical analysis to distinguish CAA from other oral tumors.

The prognostic significance of FOXP3 expression in patients with metastatic HER2-positive breast cancer

Background. The effectiveness of targeted therapy in patients with HER2+ breast cancer largely depends on the tumor microenvironment. Regulatory T-lymphocytes (FOXP3+) negatively regulate immune responses and are mostly considered a factor of unfavorable prognosis. Breast cancer is a heterogeneous disease with unique biological properties for each molecular subtype. The impact of regulatory T cells on the prognosis of HER2+ breast cancer is controversial. Purpose – to evaluate the prognostic significance of regulatory T cells in patients with metastatic HER2+ breast cancer. Materials and Methods. The study included 78 patients with HER2+ breast cancer who were treated at the Sumy Regional Clinical Oncology Center from 2014 to 2024. Data on clinical and pathological characteristics of patients were taken from the primary medical documentation. Immunohistochemistry was performed for all samples of tumor tissue. Regulatory T lymphocytes were visualized using antibodies against FOXP3. Pearson test, One-way ANOVA, Kaplan–Meier method, and logarithmic test were used for statistical analysis. The Local Ethics Committee of the Sumy Regional Clinical Oncology Center approved the study. Results. The mean age of patients with low and high Foxp3 expression was 53.1 ± 1.74 and 57.3 ± 1.64, respectively. Among patients with high Foxp3 expression, there was a high proportion of women younger than 50 years (p = 0.0423) and estrogen-negative breast cancer (χ2 = 8.4080, p = 0.023). Other clinicopathological characteristics of the patients, such as the location of the primary tumor, histopathological diagnosis, the tumor grades, visceral and non-visceral metastases, and the Ki67 proliferation index, did not show an association with Foxp3 expression. Median progression-free survival was 12.9 months and 15.5 months for patients with low and high Foxp3 expression, respectively (Log-rank p = 0,0001). Median overall survival was 21.6 months and 46.9 months for patients with low and high Foxp3 expression, respectively (Log-rank p = 0,0001). Conclusions. In patients with metastatic HER2+ breast cancer, high Foxp3 expression is associated with better progression-free and overall survival. Among those with high FOXP3 expression, women under 50 years and with estrogen-negative breast cancer are more prevalent.

Are Ki-67 and Procalcitonin Expression Levels Useful in Predicting the Biological Behavior of Hepatocellular Carcinoma After Liver Transplantation?

Background: Examinations of procalcitonin (PCT) and Ki-67 expression levels in hepatocellular carcinoma (HCC) patients who have undergone liver transplantation (LT) through immunohistochemical analyses of tumor tissue may reveal the biological characteristics of the tumor, thus informing the selection of HCC patients for LT. Methods: Hepatectomy specimens from 86 HCC patients who underwent LT were obtained and analyzed immunohistochemically for the expression of PCT and Ki-67. The percentage and intensity of PCT staining, as well as the percentage of Ki-67 expression, were assessed for each patient. The impacts of PCT and Ki-67 expression on disease-free survival, overall survival, and the recurrence rate were studied, as well as their correlations with other clinicopathological features. Results: The recurrent HCC group showed a higher Ki-67 level (p < 0.001), larger maximum dominant tumor diameter (p < 0.001), and higher rate of vascular invasion (p = 0.001). The pre-transplant AFP (p = 0.001), maximum dominant tumor diameter (p < 0.001), number of tumor nodules (p < 0.001), rate of vascular invasion (p = 0.001), and Ki-67 level (p = 0.044) were higher in patients beyond the Milan criteria. Similarly, the pre-transplant AFP (p < 0.001); maximum dominant tumor diameter (p < 0.001); number of tumor nodules (p < 0.001); rates of portal vein tumor thrombus (p = 0.002), poor differentiation (p = 0.021), and vascular invasion (p < 0.001); and Ki-67 level (p = 0.010) were higher in patients beyond the expanded Malatya criteria. The maximum dominant tumor diameter (p = 0.006); Ki-67 level (p = 0.003); rates of vascular invasion (p < 0.001), cases beyond the Milan criteria (p = 0.042) and the expanded Malatya criteria (p = 0.027), and portal vein tumor thrombus (p = 0.020); and presence of recurrence (p < 0.001) were higher in HCC patients with mortality. The Kaplan-Meier estimates indicated that Ki-67 levels exceeding 5% significantly affected DFS and OS. Although the Kaplan-Meier estimates indicated that a PCT staining percentage of ≥25% did not have a statistically significant effect on DFS or OS, the outcomes may be considered clinically significant. Conclusions: This study demonstrated that the Ki-67 proliferation index can be used as a predictive biomarker of the biological behavior of HCC. Furthermore, we claim that PCT expression over a particular threshold might impact recurrence and survival, and we believe that further multicenter prospective studies focused on standardized PCT antibody staining are crucial in order to determine its potential as a biomarker for HCC.

Differentiating low- and high-proliferative soft tissue sarcomas using conventional imaging features and radiomics on MRI

Abstract Background Soft-tissue sarcomas are rare tumors of the soft tissue. Recent diagnostic studies mainly dealt with conventional image analysis and included only a few cases. This study investigated whether low- and high-proliferative soft tissue sarcomas can be differentiated using conventional imaging and radiomics features on MRI. Methods In this retrospective study, soft tissue sarcomas were separated into two groups according to their proliferative activity: high-proliferative (Ki-67 ≥ 20%) and low-proliferative soft tissue sarcomas (Ki-67 &lt; 20%). Several radiomics features, and various conventional imaging features on MRI like tumor heterogeneity, peritumoral edema, peritumoral contrast-enhancement, percentage of ill-defined tumor margins, Apparent Diffusion Coefficient (ADC) values, and area under the curve (AUC) in contrast dynamics were collected. These imaging features were independently compared with the two mentioned groups. Results 118 sarcoma cases were included in this study. Metastases were more prevalent in high-proliferative soft tissue sarcomas (p &lt; 0.001), and time till metastasis negatively correlated with the Ki-67 proliferation index (k -0.43, p = 0.021). Several radiomics features representing intratumoral heterogeneity differed significantly between both groups, especially in T2-weighted (T2w) and contrast-enhanced T1-weighted (CE-T1w) sequences. Peritumoral contrast enhancement and edema were significantly more common in soft tissue sarcomas with a high Ki-67 index (p &lt; 0.001). Tumor configuration, heterogeneity, and ill-defined margins were commonly seen in high-proliferative soft tissue sarcomas (p = 0.001–0.008). Diffusion restriction (ADC values) and contrast dynamics (AUC values) did not present significant differences between low- and high-proliferative soft tissue sarcomas. Conclusions Several radiomics and conventional imaging features indicate a higher Ki-67 proliferation index in soft tissue sarcomas and can therefore be used to distinguish between low- and high-proliferative soft tissue sarcomas.

High-Risk MCL: Recognition and Treatment.

Significant progress in determining the molecular origins and resistance mechanisms of mantle cell lymphoma (MCL) has improved our understanding of the disease's clinical diversity. These factors greatly impact prognosis in MCL patients. Given the dynamic alterations in MCL clones and disease evolution, it is crucial to recognize high-risk prognostic factors at diagnosis and relapse. Clinical factors include a high MCL International Prognostic Index score with a high Ki-67 proliferation index; early disease progression within 24 months of first-line treatment; >3 prior lines of therapy at relapse; and an aggressive (blastoid or pleomorphic) histology. Molecular aberrations include dysregulated cyclin D1; an aberrant SOX11-CD70 axis; upregulated Musashi-2; MYC rearrangement; metabolic reprogramming; and epigenetic changes. Other factors contributing to high-risk MCL include an immune-depleted microenvironment and clone adaptability with complex chromosomal anomalies and somatic mutations in TP53, NSD2, CCND1, CDKN2A, BIRC3, SP140, KMT2D, NFkBIE, SMARCA4, and NOTCH2. Ultra-high-risk MCL is indicated by the coexistence of multiple high-risk prognostic factors in the relapse setting and can portend very short progression-free survival. As MCL treatments advance towards cellular therapies, resistance to anti-CD19 chimeric antigen receptor T-cell therapy is also observed. These findings necessitate revisiting the prognostic impact of high-risk factors, current management strategies, new bi- and tri-specific T-cell engagers, combination therapies, novel therapeutic targets, and next-generation clinical trials for high-risk MCL patients. This article provides a comprehensive update on recognizing and managing high-risk MCL, encompassing current practices and future directions.