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Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Fusión Génica , Proteínas del Citoesqueleto/genética , Proteínas Adaptadoras Transductoras de Señales/genéticaRESUMEN
Peritoneal dissemination of ovarian cancer (OC) correlates with poor prognosis, but the mechanisms underlying the escape of OC cells from the intraperitoneal immune system have remained unknown. We here identify pigment epithelium-derived factor (PEDF) as a promoting factor of OC dissemination, which functions through induction of CD206+ Interleukin-10 (IL-10)-producing macrophages. High PEDF gene expression in tumors is associated with poor prognosis in OC patients. Concentrations of PEDF in ascites and serum are significantly higher in OC patients than those with more benign tumors and correlated with early recurrence of OC patients, suggesting that PEDF might serve as a prognostic biomarker. Bromodomain and extraterminal (BET) inhibitors reduce PEDF expression and limit both OC cell survival and CD206+ macrophage induction in the peritoneal cavity. Our results thus implicate PEDF as a driver of OC dissemination and identify a BET protein-PEDF-IL-10 axis as a promising therapeutic target for OC.
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Neoplasias Ováricas , Serpinas , Proteínas del Ojo , Femenino , Humanos , Interleucina-10/metabolismo , Macrófagos/metabolismo , Factores de Crecimiento Nervioso , Neoplasias Ováricas/metabolismo , Serpinas/genética , Serpinas/metabolismoRESUMEN
Ataxia-telangiectasia mutated (ATM) functions as a key initiator and coordinator of DNA damage and cellular stress responses. ATM signaling pathways contain many downstream targets that regulate multiple important cellular processes, including DNA damage repair, apoptosis, cell cycle arrest, oxidative sensing, and proliferation. Over the past few decades, associations between germline ATM pathogenic variants and cancer risk have been reported, particularly for breast and pancreatic cancers. In addition, given that ATM plays a critical role in repairing double-strand breaks, inhibiting other DNA repair pathways could be a synthetic lethal approach. Based on this rationale, several DNA damage response inhibitors are currently being tested in ATM-deficient cancers. In this review, we discuss the current knowledge related to the structure of the ATM gene, function of ATM kinase, clinical significance of ATM germline pathogenic variants in patients with hereditary cancers, and ongoing efforts to target ATM for the benefit of cancer patients.
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Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Predisposición Genética a la Enfermedad , Neoplasias/etiología , Neoplasias/metabolismo , Animales , Apoptosis/genética , Proteínas de la Ataxia Telangiectasia Mutada/química , Ciclo Celular/genética , Roturas del ADN de Doble Cadena , Daño del ADN , Reparación del ADN , Manejo de la Enfermedad , Regulación de la Expresión Génica , Mutación de Línea Germinal , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Oxidación-Reducción , Estrés Oxidativo , Medicina de Precisión , Transducción de SeñalRESUMEN
Proximal-type epithelioid sarcoma is an aggressive malignant soft-tissue neoplasm, a "proximal" variant of epithelioid sarcoma, resistant to multimodal therapy and involved in early tumor-related death. Pertinent treatments are, therefore, continually being explored. A 24-year-old woman with nonmetastatic proximal-type epithelioid sarcoma, originating subcutaneously on the right side of the vulva, underwent surgical resection; the lesion recurred, however, leading to death 3 months after the second surgery. Here described is a case of proximal-type epithelioid sarcoma expressing L-type amino acid transporter 1 (LAT1) that transports essential amino acids and p-borono-L-phenylalanine (BPA)-the chemical compound used in boron neutron capture therapy (BNCT)-and is highly expressed in many malignant tumors. Recently, LAT1 has drawn attention, and relevant treatments have been studied-LAT1 inhibitor and BNCT. LAT1 expression in proximal-type epithelioid sarcoma may lead to cogent treatments for the disease.
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ABSTRACT: Plaque-type blue nevus is a rare variant of blue nevi that was first described in 1954. This article presents clinical, macroscopic, histopathological, and genetic findings for a case of large plaque-type blue nevus expanding into the mammary gland tissue as well as the skin of the right breast. A 63-year-old woman presented with a congenital, large, blue-colored macule limited to the hypochondriac area of the right breast. A nodule 8 mm in diameter was also present in the mammary gland tissue. Magnetic resonance imaging was unable to detect diffuse melanin deposition in the mammary gland tissue, but pigmentation in the whole mammary parenchyma was observed in the cut surfaces of the mastectomy specimen. Histopathology revealed a sparse distribution of dendritic melanocytes in whole sections of the mammary fibrous tissue and partial sections of the dermis. The histopathological criteria for atypical cellular blue nevus were fulfilled for the mammary tumor. Nodal blue nevus was diagnosed in the sentinel lymph node. Sanger sequencing confirmed the GNAQ Q209P mutation, which was also identified in all 4 literature cases of plaque-type blue nevus, but rarely in conventional blue nevi and uveal melanoma. It should be noted that plaque-type blue nevus can expand into the mammary gland tissue, even if the pigmented lesion does not exist on the overlying breast skin. The mammary condition can be the origin of primary mammary melanocytic tumors. Mosaicism of the GNAQ Q209P mutation can be a characteristic genetic alteration to extensive blue nevi, including plaque-type blue nevus.
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Neoplasias de la Mama/patología , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Nevo Azul/patología , Neoplasias Cutáneas/patología , Neoplasias de la Mama/genética , Femenino , Humanos , Persona de Mediana Edad , Mutación , Nevo Azul/genética , Neoplasias Cutáneas/genéticaRESUMEN
Synovial sarcoma is a rare tumor requiring new treatment methods. A 46-year-old woman with primary monophasic synovial sarcoma in the left thigh involving the sciatic nerve, declining surgery because of potential dysfunction of the affected limbs, received two courses of BNCT. The tumor thus reduced was completely resected with no subsequent recurrence. The patient is now able to walk unassisted, and no local recurrence has been observed, demonstrating the applicability of BNCT as adjuvant therapy for synovial sarcoma. Further study and analysis with more experience accumulation are needed to confirm the real impact of BNCT efficacy for its application to synovial sarcoma.
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Terapia por Captura de Neutrón de Boro , Sarcoma Sinovial/radioterapia , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sarcoma Sinovial/diagnóstico por imagen , Sarcoma Sinovial/cirugíaRESUMEN
Clear cell sarcoma of tendons and aponeuroses (CCS) is a rare, malignant tumor arising in lower extremities with no effective treatment other than wide surgical resection. Here described is a case of primary CCS in the peroneal tendon of the right foot of a 54-year-old woman enrolled to undergo BNCT. The tumor mass post-BNCT disappeared totally without damage to other normal tissue, demonstrating, for the first time, the potential efficacy of BNCT in complete local control of CCS.
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Terapia por Captura de Neutrón de Boro/métodos , Enfermedades del Pie/radioterapia , Sarcoma de Células Claras/radioterapia , Tendones , Biopsia con Aguja , Femenino , Enfermedades del Pie/diagnóstico por imagen , Enfermedades del Pie/patología , Humanos , Neoplasias Pulmonares/secundario , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Planificación de la Radioterapia Asistida por Computador , Sarcoma de Células Claras/diagnóstico por imagen , Sarcoma de Células Claras/secundario , Tendones/diagnóstico por imagen , Tendones/patología , Resultado del TratamientoRESUMEN
Bone metastasis has a major impact on the quality of life that general therapy cannot control. We established a bone metastasis model with a human breast cancer cell line and investigated the therapeutic effect of boron neutron capture therapy (BNCT). BNCT suppressed tumor growth in cases of intramedullary small tumors without damaging normal tissues, providing preliminary evidence that it is a potentially new therapeutic option for controlling tumor growth from bone metastasis. Further research is warranted for its clinical application.
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Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Compuestos de Boro/química , Terapia por Captura de Neutrón de Boro/métodos , Neoplasias de la Mama/patología , Fenilalanina/química , Animales , Línea Celular Tumoral , Femenino , Humanos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: The mammalian Notch family ligands delta-like 3 (DLL3) is reported to be a potential therapeutic target for large cell neuroendocrine carcinomas (LCNEC). The effect of DLL3 expression on LCNEC prognosis has not yet been elucidated. METHODS: We reviewed the medical records of 70 LCNEC patients undergoing surgical resection between 2001 and 2015 using a prospectively maintained database. We performed immunohistochemistry for DLL3 and investigated the correlation between the sensitivity of LCNEC to platinum-based adjuvant chemotherapy. RESULTS: DLL3 expression was positive in 26 (37.1%) LCNEC patients. A total of 23 patients (32.9%) received platinum-based adjuvant chemotherapy. Among patients with DLL3 expression-positive tumors, no difference was found in the five-year overall survival (OS) or recurrence-free survival (RFS) between patients with and without adjuvant chemotherapy (surgery + chemotherapy vs. surgery alone, five-year OS: 58.3% vs. 35.7% P = 0.36, five-year RFS: 41.7% vs. 35.7% P = 0.74). In contrast, among patients with DLL3-negative tumors, significantly greater five-year OS and RFS rates were observed for patients with adjuvant chemotherapy than for those without it (surgery + chemotherapy vs. surgery alone: five-year OS: 90.0% vs. 26.9% P<0.01, five-year RFS: 80.0% vs. 21.7% P < 0.01). A multivariate analysis for the RFS revealed that adjuvant chemotherapy was a significant independent prognostic factor among patients with DLL3-negative tumors (hazard ratio [HR]: 0.05, 95% confidence interval [CI]: 0.01-0.41, P < 0.01), although it was not a factor among patients with DLL3-positive tumors (HR: 0.73, 95% CI: 0.23-2.27, P = 0.58). CONCLUSIONS: Our results revealed that DLL3 is a predictive marker of sensitivity to platinum-based adjuvant chemotherapy for LCNEC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: DLL3 was a predictive marker of sensitivity to platinum-based adjuvant chemotherapy for LCNEC. Among patients with DLL3 expression-negative LCNEC, platinum-based adjuvant chemotherapy significantly improved the OS and RFS, although it did not do so among patients with DLL3 expression-positive LCNEC. WHAT THIS STUDY ADDS: Our results suggest that DLL3 expression-positive LCNEC may be better treated with other types of adjuvant chemotherapy, such as the anti-DLL3 therapies if these effects are confirmed by ongoing clinical research.
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Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma Neuroendocrino/tratamiento farmacológico , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas de la Membrana/metabolismo , Anciano , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/patología , Carcinoma Neuroendocrino/metabolismo , Carcinoma Neuroendocrino/patología , Quimioterapia Adyuvante , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: The purpose of this study was to determine the optimal regimen of neoadjuvant chemotherapy (NAC) for advanced epithelial ovarian, fallopian tube, and peritoneal cancers. METHODS: A clinical information survey involving 171 patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer was conducted. These patients underwent NAC followed by interval debulking surgery at the Hyogo Cancer Center (Hyogo, Japan) between January 2006 and December 2015. RESULTS: The median observation period was 41 (range 4-138) months. Dose-dense paclitaxel and carboplatin (TC) was administered in 101 patients (59%); tri-weekly TC was administered 70 patients (41%). Median progression-free survival was 21 [95% confidence interval (CI) 18-23] months and 15 (95% CI 13-17) months in the dose-dense TC and conventional-TC group [hazard ratio (HR) = 0.69, 95% CI 0.46-0.96; p = 0.02], respectively. The median overall survival was 59 (95% CI 46-72) and 40 (95% CI 32-57) months in the dose-dense TC group and conventional-TC group (HR = 0.72, 95% CI 0.48-1.06; p = 0.09). Multivariate analysis for progression-free survival demonstrated that dose-dense TC represented an independent prognostic factor (HR = 0.70, 95% CI 0.50-0.99; p = 0.04). CONCLUSIONS: Dose-dense TC is a promising regimen of NAC for advanced epithelial ovarian cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carcinoma Epitelial de Ovario/mortalidad , Carcinoma Epitelial de Ovario/cirugía , Procedimientos Quirúrgicos de Citorreducción , Neoplasias de las Trompas Uterinas/mortalidad , Neoplasias de las Trompas Uterinas/cirugía , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Terapia Neoadyuvante , Paclitaxel/administración & dosificación , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/cirugía , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
AIM: Expression of CD44 variant isoforms (CD44v) promotes the synthesis of reduced glutathione and contributes to reactive oxygen species defense through up-regulation of the intracellular antioxidant. The aim of the study was to investigate the expression of CD44v9 and oxidative DNA damage marker, 8-OHdG, in benign ovarian endometrioma (OE) and OE harboring clear cell carcinomas (CCC). METHODS: A retrospective study was performed at the Department of Gynecology, Nara Medical University hospital from January 2006 to December 2012. Patients with histologically confirmed benign OE (n = 27) and OE harboring areas of CCC (n = 8) were selected. Tissue samples were immunohistochemically analyzed for the presence of CD44v9 and 8-OHdG using avidin-biotin complex method. RESULTS: CD44v9 was located on the cell membrane of endometriotic epithelial cells and expressed in 88.9% (24/27) of benign OE tissues. Only 25.0% (2/8) of benign endometriotic lesions adjacent to CCC was found to stain weakly for CD44v9. Percentage of CD44v9 positive cells was 68.5 ± 20.2% (mean ± standard deviation) of benign OE, 16.7 ± 16.5% of CCC endometriotic tissue (P < 0.001). Compared to benign OE, CCC endometriotic tissue showed a significant increase in the proportion of 8-OHdG expression (77.3 ± 22.5% vs 94.9 ± 3.0%, P = 0.049). A significant negative correlation was observed between CD44v9 status and 8-OHdG nuclear expression (r = -0.458, Pâ = â0.006). CONCLUSION: Alterations in CD44v9 and 8-OHdG may be associated with malignant transformation of benign OE.
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8-Hidroxi-2'-Desoxicoguanosina/metabolismo , Adenocarcinoma de Células Claras/metabolismo , Endometriosis/metabolismo , Receptores de Hialuranos/metabolismo , Neoplasias Ováricas/metabolismo , Adulto , Biomarcadores de Tumor/metabolismo , Transformación Celular Neoplásica/metabolismo , Células Epiteliales/metabolismo , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Ovario/metabolismo , Especies Reactivas de Oxígeno , Estudios RetrospectivosAsunto(s)
Dermatofibrosarcoma/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Proteínas de Fusión Oncogénica/genética , Piel/patología , Pared Abdominal , Adulto , Dorso , Dermatofibrosarcoma/genética , Dermatofibrosarcoma/patología , Femenino , Pruebas Genéticas , Humanos , Imagen por Resonancia Magnética , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/patología , Análisis de Secuencia de ADN , Piel/diagnóstico por imagenRESUMEN
OBJECTIVE: We conducted a retrospective study to evaluate the correlation between pre-operative and post-operative histological diagnoses on endometrial cancer, and to describe the treatments and outcomes when post-operative diagnoses are downgraded from pre-operative histology. METHODS: Patients who underwent surgery for endometrial cancer in our facility between 2010 and 2013 were enrolled in the study. The definition of downgrade discordance is in accordance with the following criteria: 1) the pre-operative and post-operative histological diagnoses were both endometrioid and the final pathology was a lower grade than the pre-operative pathology and 2) the pre-operative diagnosis was not endometrioid, whereas the post-operative diagnosis was endometrioid grade 2 or less. RESULTS: A total of 250 patients were enrolled, and the concordance rates were 56% for endometrioid adenocarcinoma grade 1 (EMG1), 67% for EMG2, 67% for EMG3, 82% for carcinosarcoma, 71% for serous carcinoma, and 67% for clear cell carcinoma. Eighteen cases (6.6%) were identified as downgrade discordancy. Of the 18 patients, the triage for adjuvant therapy remained the same for 15 cases (83%), all of whom had no evidence of disease at their last visit. Three cases had discordances with respect to triage for adjuvant therapy; the therapies were triaged based on post-operative diagnosis. Of these patients one had a recurrence. CONCLUSIONS: Good correlation was observed between pre-operative and final histological diagnoses of endometrioid carcinoma (56%-67%) and type 2 carcinoma (67%-82%). Approximately 7% (18/250) of patients had downgrade discordancy; however, triage for adjuvant therapy did not change for approximately 80% (15/18) of the patients with downgrade discordancy. Further studies are needed to evaluate the effectiveness of triages that are based on post-operative diagnoses.
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Neoplasias Endometriales/diagnóstico , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/cirugía , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Femenino , Humanos , Histerectomía , Clasificación del Tumor , Estadificación de Neoplasias , Cuidados Posoperatorios , Cuidados Preoperatorios , Estudios Retrospectivos , SalpingooforectomíaRESUMEN
Three aromatic compounds, 2α,3α-epoxyflavan-5,7,4'-triol-(4ß â 8)-afzelechin (1), 2ß,3ß-epoxyflavan-5,7,4'-triol-(4α â 8)-epiafzelechin (2), and methyl 4-ethoxy-2-hydroxy-6-propylbenzoate (3), as well as eight known compounds (4-11) were isolated from the bark of Cassipourea malosana (Rhizophoraceae). Their structures were determined on the basis of an analysis of spectroscopic data. The in vitro cytotoxic activities of these compounds against human ovarian cancer cell line TOV21G were evaluated. Most compounds showed little activity; however, the methyl derivatives of flavan dimers (1a and 2a) showed higher activity (IC50 value of 30.3 and 75.4 µM) than parent compounds 1 and 2.
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Citotoxinas/uso terapéutico , Medicamentos Herbarios Chinos/química , Neoplasias Ováricas/tratamiento farmacológico , Corteza de la Planta/química , Rhizophoraceae/química , Línea Celular Tumoral , Citotoxinas/farmacología , Femenino , HumanosRESUMEN
Background: Transformed follicular lymphoma (TFL, ZC3H12D) was identified as a candidate tumor suppressor gene that contributes to cell-cycle arrest through regulation of Rb phosphorylation, but the clinical impact of TFL is unknown. The goal of this study was to evaluate the prognostic significance of TFL expression in advanced endometrial cancer.Methods: Tissue samples were obtained from 103 patients with Federation Internationale des Gynaecologistes et Obstetristes stage III-IV endometrial cancer. Associations between TFL expression and outcomes were evaluated using the Kaplan-Meier method and multivariate Cox proportional hazards regression models.Results: There were 24 TFL-low cases (23.3%) and the 10-year progression-free survival (PFS) and overall survival (OS) in these cases were lower than those for patients with normal TFL expression in univariate analysis (PFS, P = 0.003; OS, P = 0.106). In multivariate analysis, TFL status was a significant predictor for PFS [HR = 2.76; 95% confidence interval (CI), 1.45-5.28; P = 0.002] and OS (HR = 1.94; 95% CI, 0.91-4.11; P = 0.085), adjusted for covariates. The TFL gene maps to human chromosome 6q25.1, where estrogen receptor alpha (ERα) gene ESR1 is also located. Lack of ERα expression is a poor prognostic factor in early endometrial cancer. Among 41 ERα-low patients, 10-year PFS was significantly lower in 15 TFL-low cases (univariate analysis, P = 0.055; multivariate analysis, HR = 4.70; 95% CI, 1.68-13.20; P = 0.003).Conclusions: We identified TFL as a strong independent prognostic factor, regardless of ERα status.Impact: An investigation of the mechanism underlying tumor suppression by TFL may lead to new therapies for patients with advanced endometrial cancer. Cancer Epidemiol Biomarkers Prev; 27(8); 963-9. ©2018 AACR.
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Transformación Celular Neoplásica/patología , Neoplasias Endometriales/mortalidad , Linfoma Folicular/fisiopatología , Adulto , Anciano , Terapia Combinada , Neoplasias Endometriales/patología , Neoplasias Endometriales/terapia , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Transcription factor hepatocyte nuclear factor 1-beta (HNF-1ß) enhances checkpoint kinase 1 (Chk1) activation and promotes G2/M cell cycle progression in ovarian clear cell carcinoma (CCC) following exposure to diverse genotoxic agents including bleomycin. However, the underlying mechanism leading to checkpoint activation of HNF-1ß still remains largely unknown. To clarify the effects of HNF-1ß on cell cycle checkpoints, human CCC cell lines were transfected with siRNAs targeting HNF-1ß, Claspin, USP28, or a control vector. Ubiquitination and stabilization of Claspin protein by HNF-1ß was assessed by immunoprecipitation. Loss-of-function studies using RNAi-mediated gene silencing indicated that HNF-1ß facilitated the Claspin expression after treatment with a genotoxic agent bleomycin, resulting in accumulation of phosphorylated Chk1 (p-Chk1) and promotion of survival in CCC cell lines. This study showed for the first time that USP28, a de-ubiquitinase crucial for Claspin expression, is one target gene of HNF-1ß. Knockdown of endogenous USP28 suppressed the Claspin expression and p-Chk1 activation and cell viability. Our findings identify a novel pathway of the HNF-1ß-USP28-Claspin-Chk1 axis in checkpoint signal amplification in response to DNA damage. Targeting this pathway may represent a putative, novel, anticancer strategy in ovarian CCC.
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BACKGROUND: Malignancy during pregnancy has become a significant cause of maternal death in developed countries, likely due to both an older pregnant population, and increases of cervical cancer in younger women. Our aim is to investigate the clinical aspects of malignancy during pregnancy in Japan and to use this information to identify opportunities for earlier detection and treatment. METHODS: We provided a questionnaire to 1508 secondary or tertiary care hospitals in Japan. We reviewed the clinical characteristics of cases with malignancy during pregnancy for the period of January to December, 2008. From the 760 institutions which responded, we obtained clinical information for 227 unique cases. The questionnaire provided clinical information, including disease site, pregnancy outcome and how the disease was detected. RESULTS: The most common type of malignancy was cervical cancer (n = 162, 71.4%) followed by ovarian (n = 16, 7.0%) and breast cancer (n = 15, 6.6%). Leukemia (n = 7, 3.1%), colon cancer (n = 5, 2.2%), gastric cancer (n = 5, 2.2%), malignant lymphoma (n = 4, 1.8%), thyroid cancer (n = 3, 1.3%), brain cancer (n = 3, 1.3%), endometrial cancer (n = 2, 0.9%), and head and neck cancer (n = 2, 0.9%) accounted for the remaining cases. Overall, gynecological malignancies accounted for 79.3% (95% confidence interval 74.0-84.6) of pregnancy associated malignancies diagnosed in the present study. The majority of cervical cancers, 149 (92.0%) of 162, were diagnosed by a Pap (Papanicolaou) smear during early gestation. Ten (62.5%) of the ovarian cancer cases were diagnosed by ultrasonography during a prenatal checkup or at the time of initial pregnancy diagnosis. Out of 14 breast cancers, only one (7.1%) was diagnosed by screening breast exam. CONCLUSIONS: From this study, we reaffirm the clear and significant benefits of prenatal checkups starting at an early gestational age for the detection of gynecological cancers during pregnancy. Conversely, breast cancer detection during pregnancy was poor, suggesting new strategies for early identification of this disease are required.