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BACKGROUND AND OBJECTIVES: The objective of this study is to establish the detection rate of sentinel lymph node (SLN) biopsies and to determine the sensitivity and false-negative rate of SLN biopsies compared with those of systematic pelvic and para-aortic lymphadenectomies in endometrial cancer. METHODS: This prospective cohort study enrolled patients with endometrial cancer who were scheduled for surgical staging. Patients with a history of chemotherapy or radiotherapy, an abnormal liver function test, or an allergy to indocyanine green (ICG) were excluded. All patients underwent surgical staging with an ICG injection at the cervix. SLNs were identified by a near-infrared fluorescent camera. All SLNs were sent to a pathologist for ultrastaging. RESULTS: From November 2019 to June 2023, 142 patients underwent SLN mapping and surgical staging. SLNs were not detected bilaterally in 8 patients. The detection rate of the SLN biopsies in this study was 91.2%. Thus, the accuracy of the SLN biopsies was 97.6%. The sensitivity for finding metastatic SLNs was 84.2%, with a negative predictive value of 97.22%. CONCLUSIONS: A SLN biopsy in endometrial cancer has a high detection rate and high accuracy. However, surgical expertise and a learning curve are required.
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Neoplasias Endometriales , Laparoscopía , Ganglio Linfático Centinela , Humanos , Femenino , Biopsia del Ganglio Linfático Centinela/métodos , Ganglio Linfático Centinela/diagnóstico por imagen , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patología , Estudios Prospectivos , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/cirugía , Escisión del Ganglio Linfático , Verde de Indocianina , Laparoscopía/métodos , Imagen Óptica/métodos , Ganglios Linfáticos/patología , Estadificación de NeoplasiasRESUMEN
Triple negative breast cancer (TNBC) lacks targeted treatment resulting in poor prognosis. Targeting overexpressing mesothelin (MSLN) using MSLNspecific T cells is an attractive treatment approach and the aim of the present study. The expression of MSLN in human TNBC paraffin sections was analyzed by immunohistochemistry. Lentiviral vector harbored granulocytemacrophage colony stimulating factor (GMCSF), interleukin4 (IL4) and MSLN cDNAs was constructed to generate selfdifferentiated myeloidderived antigenpresentingcells reactive against tumor expressing MSLN dendritic cell (MSLNSmartDC) for MSLNspecific T cell activation. The results showed high MSLN in 32.8% of all breast cancer subtypes and 57% in TNBC. High MSLN was significantly associated with TNBC subtype and the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. MSLNSmartDC exhibited comparable phenotype to DC generated by exogenous cytokine treatment and an addition of 40s ribosomal protein subunit 3 (RPS3), a tolllike receptor 4 ligand, enhanced DC maturation and function by upregulation of CD40, CD80 and CD83 expressions and IL12p70 secretion. MSLNspecific CD8+CD69+ IFNγ+ T cells were detected in T cells activated by both MSLNSmartDC and RPS3MSLNSmartDC. MSLNspecific T cells activated by these DCs showed more specific killing capability against naturally expressed MSLNHCC70 and artificially MSLNoverexpressing MDAMB231 compared with parental MDAMB231 in both two dimensional (2D) and 3Dculture systems. In conclusion, the results demonstrated the efficacy of MSLNSmartDC to promote MSLNspecific T cells response against TNBC and RPS3 can enhance the cytolytic activity of these T cells providing an alternative treatment approach for patients with TNBC.
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Células Dendríticas , Mesotelina , Proteínas Ribosómicas , Linfocitos T , Neoplasias de la Mama Triple Negativas , Línea Celular Tumoral , Células Dendríticas/metabolismo , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Humanos , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Linfocitos T/inmunología , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Women with chronic abnormal uterine bleeding-ovulatory dysfunction (AUB-O) are at increased risk of endometrial neoplasia. We conducted a non-inferiority randomized controlled trial to determine the effectiveness of two cyclic-progestin regimens orally administered 10 d/month for 6 months on endometrial protection and menstruation normalization in women with AUB-O. There were 104 premenopausal women with AUB-O randomized to desogestrel (DSG 150 µg/d, n = 50) or medroxyprogesterone acetate (MPA 10 mg/d, n = 54) group. Both groups were comparable in age (44.8 ± 5.7 vs. 42.5 ± 7.1 years), body mass index (24.8 ± 4.7 vs. 24.9 ± 4.7 kg/m2), and AUB characteristics (100% irregular periods). The primary outcome was endometrial response rate (the proportion of patients having complete pseudodecidualization in endometrial biopsies during treatment cycle-1). The secondary outcome was clinical response rate (the proportion of progestin withdrawal bleeding episodes with acceptable bleeding characteristics during treatment cycle-2 to cycle-6). DSG was not inferior to MPA regarding the endometrial protection (endometrial response rate of 78.0% vs. 70.4%, 95% CI of difference - 9.1-24.4%, non-inferiority limit of - 10%), but it was less effective regarding the menstruation normalization (acceptable bleeding rate of 90.0% vs 96.6%, P = 0.016).Clinical trial registration: ClinicalTrials.gov (NCT02103764, date of approval 18 Feb 2014).
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Desogestrel/administración & dosificación , Endometrio/efectos de los fármacos , Acetato de Medroxiprogesterona/administración & dosificación , Menstruación/efectos de los fármacos , Ovario/efectos de los fármacos , Ovulación/efectos de los fármacos , Progestinas/administración & dosificación , Hemorragia Uterina/tratamiento farmacológico , Adulto , Desogestrel/efectos adversos , Método Doble Ciego , Endometrio/fisiopatología , Femenino , Humanos , Acetato de Medroxiprogesterona/efectos adversos , Persona de Mediana Edad , Ovario/fisiopatología , Progestinas/efectos adversos , Estudios Prospectivos , Tailandia , Factores de Tiempo , Resultado del Tratamiento , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/fisiopatologíaRESUMEN
Breast cancer cell lines are widely used as an in vitro system with which to study the mechanisms underlying biological and chemotherapeutic resistance. In the present study, two novel breast cancer cell lines designated as PCB142CA and PCB148CA were successfully established from HER2positive and triplenegative (TN) breast cancer tissues. The cell lines were characterized by cytokeratin (CK), αsmooth muscle actin (αSMA), fibroblastactivation protein (FAP) and programmed deathligand 1 (PDL1). Cell proliferation was assessed using a colony formation assay, an MTS assay, 3dimensional (3D) spheroid and 3D organoid models. Wound healing and Transwell migration assays were used to explore the cell migration capability. The responses to doxorubicin (DOX) and paclitaxel (PTX) were evaluated by 3D spheroids. The results showed that the PCB142CA and PCB148CA cell lines were αSMAnegative, FAPnegative, CKpositive and PDL1positive. Both cell lines were adherent with the ability of 3Dmulticellular spheroid and organoid formations; invadopodia were found in the spheroids/organoids of only PCB148CA. PCB142CA had a faster proliferative but lower metastatic rate compared to PCB148CA. Compared to MDAMB231, a commercial TN breast cancer cell line, PCB148CA had a similar CD44+/CD24 stemness property (96.90%), whereas only 8.75% were found in PCB142CA. The mutations of BRCA1/2, KIT, PIK3CA, SMAD4, and TP53 were found in PCB142CA cells related to the resistance of several drugs, whereas PCB148CA had mutated BRCA2, NRAS and TP53. In conclusion, PCB142CA can serve as a novel HER2positive breast cancer cell line for drug resistance studies; while PCB148CA is a novel TN breast cancer cell line suitable for metastatic and stemnessrelated properties.
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Línea Celular Tumoral/patología , Fragmentos de Péptidos , Receptor ErbB-2 , Neoplasias de la Mama Triple Negativas/patología , Movimiento Celular , Proliferación Celular , Doxorrubicina/farmacología , Femenino , Humanos , Persona de Mediana Edad , Células Madre Neoplásicas/patología , Organoides/patología , Paclitaxel/farmacología , Esferoides Celulares/patología , Células Tumorales Cultivadas/patologíaRESUMEN
The tumor microenvironment composed of a mixture of stromal cells and their secretions has a marked impact on cancer progression. In particular, soluble factors and metabolites contribute to malignancy through the dysregulation of autophagy in cancer cells. The present study investigated the effects of ovarian cancerassociated fibroblasts (OVCAFs) with their secretory substances on the autophagy and migration of ovarian cancer cells. The conditionedmedium (CM) of OVCAFs isolated from fresh human ovarian cancer tissues was analyzed for the levels of 27 common cytokines/chemokines using a cytokine array. Autophagy in cancer cells was assessed by determining the expression of the vacuolar form of LC3 by western blot analysis and immunofluorescence. Cancer cell migration was assessed by Transwell migration assay. Interleukin (IL)8 was found to be the most highly upregulated cytokine among the cytokines/chemokines found in the OVCAFCM. The role of IL8 in ovarian cancer cell migration and its mechanistic link with autophagy was investigated. Recombinant human IL8 (rhIL8) stimulated the migration of SKOV3 and Kuramochi ovarian cancer cells, and concurrently downregulated basal autophagy, in concentrationdependent manner. Compared to the CM of control counterpart normal fibroblasts isolated from benign ovaries (OVNFCM), the CM from 3 OVCAF isolates (namely, OVCAF9, 20 and 43) exerted effects similar to rhIL8 on both cancer cell lines. The pharmacological induction of autophagy with rapamycin or metformin attenuated the promigratory effects of IL8. Neutralizing antiIL8 antibody counteracted the inhibitory effect of OVCAFCM on basal autophagy. On the whole, the present study highlights the involvement of IL8 released by CAFs in the ovarian tumor microenvironment in promoting cancer cell migration through the suppression of autophagy.
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Fibroblastos Asociados al Cáncer/metabolismo , Interleucina-8/metabolismo , Neoplasias Ováricas/metabolismo , Regulación hacia Arriba , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Medios de Cultivo Condicionados/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-8/farmacología , Metformina/farmacología , Proteínas Asociadas a Microtúbulos/metabolismo , Sirolimus/farmacología , Microambiente Tumoral , Regulación hacia Arriba/efectos de los fármacosRESUMEN
One-hundred fourty pure dysgerminomas were evaluated with particular focus on the microscopic features as seen in 125 cases with available slides. The patients ranged from 8 to 59 years of age (mean, 24.1 y). The tumors, bilateral in 4% of the cases and with a mean tumor diameter of 13 cm, were typically soft, lobulated, homogeneous, and creamy white to tan to yellow but necrosis was found in 13%, hemorrhage in 20%, and focal cystic change in 15%. On microscopic examination, the patterns and other notable features encountered, including their frequency, were as follows: an alveolar pattern resulting from delicate fibrovascular septa (51%), diffuse (33%), macronodular (14%), insular (26%), cords (28%), solid tubular (17%), microspaces (sometimes simulating glands) (12%), follicle-like spaces (5%), prominent fibrous bands (65%), stromal edema (56%), stromal luteinization (9%), granulomatous infiltrate (46%), lymphocytic infiltrate (100%), Langhans cell type giant cells (35%), syncytiotrophoblast giant cells (6%), prominent population of cells with pale to clear cytoplasm (73%), cells with amphophilic to eosinophilic cytoplasm (53%) and vacuolated occasionally signet ring-like cells (7%). Various constellations of the above findings often resulted in an appearance different from that usually portrayed in the literature and certain tumors of very different nature being in the differential such as undifferentiated carcinoma not otherwise specified, small cell carcinoma of hypercalcemic type, and malignant lymphoma. The correct diagnosis can be arrived at by considering the usual relative youth of the patient, often rather characteristic gross features, and most crucially careful attention to the microscopic features and awareness of variant morphologic findings. Those that are particularly problematic based on this study are diffuse growth with inconspicuous fibrovascular septa, macronodules, cords, solid tubular formations, spaces ranging from small to large, and mimicking glands or follicles, prominent fibrous to edematous stroma, and cells with amphophilic to eosinophilic cytoplasm. According to the degree of difficulty and confidence of the interpreter, well-known immunohistochemical features of dysgerminoma, which largely differ from those of other neoplasms in the differential, will aid if felt indicated.
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Disgerminoma/patología , Neoplasias Ováricas/patología , Adolescente , Adulto , Niño , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND/AIM: Holocarboxylase synthetase (HLCS) catalyzes the specific attachment of biotin onto biotin-dependent carboxylases (BDCs) which play important roles in intermediary metabolism. Previous studies show that BDCs are overexpressed in many cancer types. However, expression of HLCS in cancerous tissues has not been reported. MATERIALS AND METHODS: Immunohistochemistry was used to investigate HLCS expression in breast tissue obtained from 65 Thai patients, and the correlation between its expression and key clinical-pathological parameters was assessed. The role of HLCS in supporting invasion was investigated in HLCS-knockdown MCF-7 cells. RESULTS: Overexpression of HLCS was significantly associated with metastasis of breast cancer cells to other lymph nodes but not the sentinel and axillary lymph nodes - a finding supported in cellular invasion assays using HLCS knockdown cells. Furthermore, overexpression of HLCS reduced survival time of patients with breast cancer. CONCLUSION: HLCS appears to be a prognostic marker for patients with breast cancer.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Ligasas de Carbono-Nitrógeno/genética , Metástasis Linfática/genética , Mama/patología , Línea Celular Tumoral , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Células MCF-7 , PronósticoRESUMEN
Cancer stem cells (CSCs) underpin the resistance of breast cancer (BC) cells to therapy. Dendritic cell (DC)-based treatment is efficacious and safe, but the efficiency of this technique for targeting CSCs in BC treatment requires further investigation. The present study aimed to investigate the ability of DCs pulsed with breast CSC antigens to activate effector lymphocytes for killing BC cells. CD44+/CD24- CSCs were isolated from BCA55-121, an in-house patient-derived BC cell line, and acquisition of stemness properties was confirmed by upregulated expression of OCT4A and a superior proliferative capacity in colony formation assays compared with whole population of BCA55-121 (BCA55-121-WP). DCs were differentiated from monocytes from peripheral blood of healthy donors and pulsed with CSC total RNA. Maturation of the CSC RNA-pulsed DCs was confirmed by increased expression of CD11c, CD40, CD83, CD86 and HLA-DR, as well as reduced CD14 expression compared with monocytes. Total lymphocytes co-cultured with CSC RNA-pulsed DCs were analyzed by flow cytometry for markers including CD3, CD4, CD8, CD16 and CD56. The results revealed that the co-cultures contained mostly cytotoxic CD8+ T lymphocytes followed by CD4+ T lymphocytes and smaller populations of natural killer (NK) and NKT cells. ELISA was used to measure IFN-γ production, and it was revealed that activated CD4+ and CD8+ lymphocytes produced more IFN-γ compared with naïve T cells, suggesting that CD8+ T cells were effector T cells. CSC RNA was a more efficient antigen source compared with RNA from mixed BC cells for activating tumor antigen-specific killing by T cells. These CSC-specific effector T cells significantly induced BC cell apoptosis at a 20:1 effector T cell:tumor cell ratio. Of note, the breast CSCs cultures demonstrated resistance to effector T cell killing, which was in part due to increased expression of programmed death ligand 1 in the CSC population. The present study highlights the potential use of CSC RNA for priming DCs in modulating an anticancer immune response against BC.
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AIM: To determine the prevalence of fallopian tube high-grade serous carcinoma (HGSC) and to analyze the benefit of the sectioning and extensively examining the fimbriated end (SEE-FIM) protocol. METHODS: Fallopian tubes from 450 patients with risk-reducing salpingo-oophorectomy, or tumor of the ovary, endometrium, fallopian tube or peritoneum were examined using the SEE-FIM protocol. Microscopic tubal pathology and the number of paraffin blocks used were evaluated. Immunostaining for p53 was performed to confirm TP53 mutation. Cost effectiveness was determined by equation of incremental cost-effectiveness ratio. RESULTS: Tubal HGSC were detected in 25 out of 70 cases of pelvic extrauterine HGSC, in 1 case of endometrioid carcinoma, and 4 cases of uterine serous carcinoma out of 250 cases of endometrial neoplasm. The mean number of tissue blocks per case was 6. The incremental cost for detecting one case of coexisting fallopian tube HGSC in the study population was 94 Thai baht/3 USD per case. CONCLUSION: The SEE-FIM protocol facilitates identification of lesions that are not distinguishable by classical sampling protocol, and this results in more accurate tumor staging and a better understanding of the carcinogenesis. The benefit of the SEE-FIM protocol was demonstrated, especially in cases at high risk for coexisting fallopian tube carcinoma.
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Cistadenocarcinoma Seroso/cirugía , Neoplasias de las Trompas Uterinas/cirugía , Trompas Uterinas/cirugía , Ovariectomía/métodos , Salpingectomía/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cistadenocarcinoma Seroso/patología , Neoplasias de las Trompas Uterinas/patología , Trompas Uterinas/patología , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Paclitaxel (PTX) is a potent anti-cancer drug commonly used for the treatment of advanced breast cancer (BCA) and melanoma. Toll-like receptor 4 (TLR4) promotes the production of pro-inflammatory cytokines associated with cancer chemoresistance. This study aims to explore the effect of TLR4 in PTX resistance in triple-negative BCA and advanced melanoma and the effect of compound A (CpdA) to attenuate this resistance. METHODS: BCA and melanoma cell lines were checked for the response to PTX by cytotoxic assay. The response to PTX of TLR4-transient knockdown cells by siRNA transfection was evaluated compared to the control cells. Levels of pro-inflammatory cytokines, IL-6 and IL-8, and anti-apoptotic protein, XIAP were measured by real-time PCR whereas the secreted IL-8 was quantitated by ELISA in TLR4-transient knockdown cancer cells with or without CpdA treatment. The apoptotic cells after adding PTX alone or in combination with CpdA were detected by caspase-3/7 assay. RESULTS: PTX could markedly induce TLR4 expression in both MDA-MB-231 BCA and MDA-MB-435 melanoma cell lines having a basal level of TLR4 whereas no significant induction in TLR4-transient knockdown cells occurred. The siTLR4-treated BCA cells revealed more dead cells after PTX treatment than that of mock control cells. IL-6, IL-8 and XIAP showed increased expressions in PTX-treated cells and this over-production effect was inhibited in TLR4-transient knockdown cells. Apoptotic cells were detected higher when PTX and CpdA were combined than PTX treatment alone. Isobologram exhibited the synergistic effect of CpdA and PTX. CpdA could significantly decrease expressions of IL-6, XIAP and IL-8, as well as excreted IL-8 levels together with reduced cancer viability after PTX treatment. CONCLUSIONS: The acquired TLR4-mediated PTX resistance in BCA and melanoma is explained partly by the paracrine effect of IL-6 and IL-8 released into the tumor microenvironment and over-production of anti-apoptotic protein, XIAP, in BCA cells and importantly CpdA could reduce this effect and sensitize PTX-induced apoptosis in a synergistic manner. In conclusion, the possible impact of TLR4-dependent signaling pathway in PTX resistance in BCA and melanoma is proposed and using PTX in combination with CpdA may attenuate TLR4-mediated PTX resistance in the treatment of the patients.
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Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Melanoma/tratamiento farmacológico , Paclitaxel/uso terapéutico , Transducción de Señal , Receptor Toll-Like 4/fisiología , Tiramina/análogos & derivados , Acetatos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Melanoma/metabolismo , Receptor Toll-Like 4/metabolismo , Microambiente Tumoral , Tiramina/fisiología , Tiramina/uso terapéuticoRESUMEN
OBJECTIVE: To determine the prevalence of patients with CIN1 or less from LEEP specimens in patients with colposcopic biopsy proven CIN2 or 3. MATERIALS AND METHODS: This study was a retrospective-descriptive chart review. Clinical data were retrieved from medical records of women with CIN2 or 3 from colposcopic biopsy who subsequently underwent LEEP procedure between 2004 and 2014. All pathological slides were reviewed by the gynecologic pathologist. Statistical analyses were performed. RESULTS: Of 210 patients, 14 patients were excluded from the study. 196 patients were in eligible criteria and data were analyzed. There were 32 patients (16.3%) with CIN1 or less from LEEP specimens who previously had colposcopic biopsies proven CIN2 or 3. Only CIN2 from biopsy was the statistically significant risk factor of CIN1 or less in LEEP specimens. Odds ratio was 10.45 (95% confidence interval: 3.28-33.33, P < 0.001). CONCLUSION: The prevalence of patients with CIN1 or less from LEEP specimens who previously had colposcopic biopsies proven CIN2 or 3 was 16.3%. CIN2 from biopsy was the statistically significant risk factor of CIN1 or less in LEEP specimens.
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Cuello del Útero/patología , Colposcopía/métodos , Conización/métodos , Electrocirugia/métodos , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adulto , Cuello del Útero/cirugía , Femenino , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/cirugía , Displasia del Cuello del Útero/cirugíaRESUMEN
INTRODUCTION: The influence of cancer-associated fibroblasts (CAFs) and high mobility group box 1 (HMGB1) has been recognized in several cancers, although their roles in breast cancer are unclear. The present study aimed to determine the levels and prognostic significance of α-smooth muscle actin-positive (ASMA+) CAFs, plus HMGB1 and receptor for advanced glycation end products (RAGE) in cancer cells. MATERIALS AND METHODS: A total of 127 breast samples, including 96 malignant and 31 benign, were examined for ASMA, HMGB1, and RAGE by immunohistochemistry. The χ2 test and Fisher's exact test were used to test the association of each protein with clinicopathologic parameters. The Kaplan-Meier method or log-rank test and Cox regression were used for survival analysis. RESULTS: ASMA+ fibroblast infiltration was significantly increased in the tumor stroma compared with that in benign breast tissue. The levels of cytoplasmic HMGB1 and RAGE were significantly greater in the breast cancer tissue than in the benign breast tissues. High ASMA expression correlated significantly with large tumor size, clinical stage III-IV, and angiolymphatic and perinodal invasion. In contrast, increased cytoplasmic HMGB1 correlated significantly with small tumor size, pT stage, early clinical stage, luminal subtype (but not triple-negative subtype), and estrogen receptor and progesterone receptor expression. The levels of ASMA (hazard ratio, 14.162; P = .010) and tumor cytoplasmic HMGB1 (hazard ratio, 0.221; P = .005) could serve as independent prognostic markers for metastatic relapse in breast cancer patients. The ASMA-high/HMGB1-low profile provided the most reliable prediction of metastatic relapse. CONCLUSION: We present for the first time, to the best of our knowledge, the potential clinical implications of the combined assessment of ASMA+ fibroblasts and cytoplasmic HMGB1 in breast cancer.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Fibroblastos Asociados al Cáncer/patología , Carcinoma Ductal de Mama/patología , Proteína HMGB1/biosíntesis , Actinas/metabolismo , Adulto , Anciano , Antígenos de Neoplasias/análisis , Antígenos de Neoplasias/biosíntesis , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/mortalidad , Femenino , Proteína HMGB1/análisis , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Proteínas Quinasas Activadas por Mitógenos/análisis , Proteínas Quinasas Activadas por Mitógenos/biosíntesis , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
OBJECTIVE: To study the correlation of endometrial pathology, which were derived from manual vacuum aspiration (MVA) and sharp metal curettage (SMC). MATERIAL AND METHOD: Women aged over 35 years old who presented with abnormal uterine bleeding were enrolled. Endometrial biopsy using MVA and sharp metal curettage under paracervical nerve block were performed, respectively. Correlation of endometrial pathology from both methods and correlation between endometrial pathology from MVA and the most severe pathology were analyzed using Kappa statistics. RESULTS: One hundred and thirty two women were enrolled Nine cases were drop out because of inability to pass the MVA's cannula through the cervical os. Mean age was 49.3 ± 8.5 years old. Mean BMI was 25.1 ± 4 kg/m². Pathological correspondence between tissue obtained from MVA and sharp metal curette was 64.2% and the Kappa agreement was 0.56 (K0 = 0.56, p-value < 0.05). Pathological correspondence between tissue obtained from MVA and the most severe pathology was 92.7% and the Kappa.agreement was 0.86 (K = 0.86, p-value < 0.05). MVA could diagnose all cases of malignancy and endometrial hyperplasia. CONCLUSION: Manual vacuum aspiration (MVA) can be used as an alternative diagnostic procedure in women with abnormal uterine bleeding.
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Biopsia/métodos , Endometrio/patología , Hemorragia Uterina/patología , Adulto , Anciano , Anciano de 80 o más Años , Anestesia Obstétrica , Femenino , Humanos , Persona de Mediana Edad , Tailandia , Vacio , Legrado por Aspiración/métodosRESUMEN
BACKGROUND: To evaluate the rate of pathologic high-risk factors, intermediate-risk factors, and treatment outcomes in early-stage cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy (RHPL). MATERIALS AND METHODS: Medical records of stage IA-IIA1 cervical cancer patients who underwent RHPL during the 2006 to 2012 time period and patient follow-up data until December 2013 were reviewed. RESULTS: Of 331 patients, 52 women (15.7%) had pathologic high-risk factors and 59 women (17.8%) had intermediate-risk factors without high-risk factors. All studied patients had an initial complete response. At median follow-up time of 40.9 months (range 1-103.3 months) and mean follow-up time of 43.3±25.3 months, 37 women had disease recurrence and 4 women had died of disease. The most common site of recurrence was the pelvis (64.8%). Five- year and 10-year disease free survival rates were 96.1% and 91.5%, respectively. Five-year and 10-year overall survival rates were 100% and 99.4%, respectively. Independent factors related to recurrence were pelvic node metastasis (odds ratio [OR], 2.670; 95%CI, 1.001-7.119), and >1/3 cervical stromal invasion (OR, 3.763; 95%CI, 1.483-9.549). CONCLUSIONS: The rates of pathologic high-risk and intermediate-risk factors should be considered and disclosed when counseling patients regarding primary treatment by RHPL. Oncologic outcomes of primary surgical treatment for early-stage cervical carcinoma were found to be excellent.
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Adenocarcinoma/patología , Carcinoma de Células Escamosas/patología , Histerectomía/mortalidad , Escisión del Ganglio Linfático/mortalidad , Neoplasias Pélvicas/patología , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/cirugía , Femenino , Estudios de Seguimiento , Hospitales Universitarios , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pélvicas/mortalidad , Neoplasias Pélvicas/cirugía , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/cirugíaRESUMEN
Pyruvate carboxylase (PC) is an anaplerotic enzyme that catalyzes the carboxylation of pyruvate to oxaloacetate, which is crucial for replenishing tricarboxylic acid cycle intermediates when they are used for biosynthetic purposes. We examined the expression of PC by immunohistochemistry of paraffin-embedded breast tissue sections of 57 breast cancer patients with different stages of cancer progression. PC was expressed in the cancerous areas of breast tissue at higher levels than in the non-cancerous areas. We also found statistical association between the levels of PC expression and tumor size and tumor stage (P < 0.05). The involvement of PC with these two parameters was further studied in four breast cancer cell lines with different metastatic potentials; i.e., MCF-7, SKBR3 (low metastasis), MDA-MB-435 (moderate metastasis) and MDA-MB-231 (high metastasis). The abundance of both PC mRNA and protein in MDA-MB-231 and MDA-MB-435 cells was 2-3-fold higher than that in MCF-7 and SKBR3 cells. siRNA-mediated knockdown of PC expression in MDA-MB-231 and MDA-MB-435 cells resulted in a 50% reduction of cell proliferation, migration and in vitro invasion ability, under both glutamine-dependent and glutamine-depleted conditions. Overexpression of PC in MCF-7 cells resulted in a 2-fold increase in their proliferation rate, migration and invasion abilities. Taken together the above results suggest that anaplerosis via PC is important for breast cancer cells to support their growth and motility.
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Neoplasias de la Mama/metabolismo , Movimiento Celular , Proliferación Celular , Piruvato Carboxilasa/metabolismo , Regulación hacia Arriba , Neoplasias de la Mama/patología , Femenino , Humanos , Células MCF-7 , Invasividad Neoplásica , Piruvato Carboxilasa/genéticaRESUMEN
BACKGROUND: To evaluate treatment outcomes of patients with stage I-III endometrial cancer treated with postoperative radiation. MATERIALS AND METHODS: A retrospective review of 166 endometrial cancer patients, undergoing surgery and postoperative radiotherapy at Siriraj Hospital from 2005-2008 was performed. Pathology was reviewed. Results of treatment were reported with 5-year loco-regional recurrence free survival (LRRFS), 5-year overall survival (OS), patterns of failure and toxicity, and according to stage and risk groups. RESULTS: Median follow up time was 62.8 months. Pathological changes were found in 36.3% of the patients after central reviews, leading to 19% changes in risk groups. Most of the patients (83.7%) received pelvic radiation (PRT) and vaginal brachytherapy (VBT). Five-year LRRFS and OS of all patients were 94.9% and 85.5%, respectively. There was no recurrence or death in low and low-intermediate risk groups. For the high-intermediate risk group, 5-year LRRFS and OS were 96.2% and 90.8%, respectively, and for the high risk group 90.5% and 71%. Late grade 3 and 5 gastrointestinal toxicity was found in 3% and 1.2% of patients, respectively. All of them received PRT 5,000 cGy in 25 fractions. CONCLUSIONS: Low and intermediate risk patients had good results with surgery and adjuvant radiation therapy. For high risk patients, postoperative radiation therapy alone appeared to be inadequate as the most common pattern of failure was distant metastasis.
Asunto(s)
Neoplasias Endometriales/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Dosificación Radioterapéutica , Radioterapia Adyuvante , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
AIM: To evaluate the agreement between colposcopic diagnosis and cervical pathology a retrospective chart review was performed. MATERIALS AND METHODS: This study included 437 patients who underwent colposcopy and cervical biopsy or conization at Siriraj Hospital from October 2010 - December 2012. The patient clinical characteristics, cervical cytology results, colposcopic diagnoses, cervical pathology results were recorded and correlations between variables were analyzed. RESULTS: Agreement of colposcopic diagnosis and cervical pathology was matched in 253 patients (57.9%). The strength of agreement with weighted Kappa statistic was 0.494 (p<0.001). Colposcopic diagnoses more often overestimated (31.1%) than underestimated (11%) the cervical pathology. Agreement of colposcopic diagnosis and cervical pathology within 1 grade was found in 411 patients (94.1%). Positive predictive value (PPV) of high grade colposcopy or more was 75.5%, whereas the negative predictive value (NPV) of insignificant and low grade colposcopy was 83.8%. False positives of high grade colposcopy or more were 21%. False negatives of insignificant or low grade colposcopy were 19.1%. CONCLUSIONS: Strength of agreement between colposcopic diagnosis and cervical pathology was found to be only moderate. A biopsy at colposcopy should be performed at a gold standard level to detect high grade lesions.
Asunto(s)
Cuello del Útero/patología , Colposcopía , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adulto , Biopsia , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Hospitales , Humanos , Metaplasia/patología , Pólipos/patología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tailandia , Cervicitis Uterina/patologíaRESUMEN
Extramedullary hematopoiesis (EMH) is the presence of hematopoietic precursors outside the bone marrow. This condition is usually associated with hematologic disorders. Although EMH can be found in almost every site in the body, female genital tract involvement is rare. The authors report EMH in the uterine cervix from a 64-year-old patient following cervical biopsy due to abnormal cervical cytology. Neither neoplasm nor hematologic disorder was detected before the diagnosis and after 1 year of follow up. To the best of our knowledge, this is the first reported case of EMH involving the uterine cervix which showed an association with tissue repair.
RESUMEN
Metaplastic carcinoma of the breast refers to a heterogenous group of mammary carcinomas that contain a mixture of various cell types, including squamous cells, spindle cells and/or a mesenchymal component, such as bone or cartilage. To the best of our knowledge, the clinical course of a tumour that has undergone a transformation from one type of metaplastic carcinoma to another subtype has not previously been reported. The present study reports the five-year clinical and pathological course of a metaplastic breast carcinoma in a 55-year-old female, who was diagnosed with a sclerosing fibroadenomatous nodule with osseous metaplasia and focal atypia. A recurrent tumour was documented four years later, showing a predominant component of osteosarcoma with adenosquamous carcinoma. Upon pathological review of the initial mass, the diagnosis was changed to low-grade adenosquamous carcinoma. The patient was treated with breast conserving therapy. However, one year later, a recurrent metaplastic carcinoma with spindle cell morphology was documented and surgically removed by mastectomy. Subsequently, pulmonary invasion of the chest wall occurred and the patient eventually succumbed due to the invasive nature of the disease.
RESUMEN
Peritoneal malignant mesothelioma (PMM) is less commonly found in female than male. The most important differential diagnosis of PMM in female patient is primary ovarian carcinoma because of their similar symptoms e.g. dyspepsia, abdominal discomfort from ascites, palpable abdominal mass, etc. However common clinical presentation of PMM is diffuse spread of peritoneal lesions without dominating tumor mass while primary ovarian tumor usually presents with large pelvic mass and smaller exta-ovarian metastatic lesions. The surgeon may make a provisional intraoperative diagnosis of PMM if both ovaries are clearly identified Unfortunately, both conditions frequently elicit fibrosis and adhesion that the exact location or the origin of tumor cannot be clearly stated. Histopathologic diagnosis of PMM is also difficult because it has three patterns of histopathology as biphasic tumors composed of epithelial and sarcomatous components or it may be monophasic of either type. When only the epithelial component is found, serous ovarian carcinoma is the important differential diagnosis while the biphasic mesothelioma must be differentiated from malignant mesodermal mixed tumor or carcinosarcoma of the ovary. The pathologist generally requires immunohistochemical study to achieve a correct diagnosis. The clinical feature and detailed histopathologic findings of the patient with PMM will be discussed