Breast Neoplasms: Papadopoulos N

Limberis V, Romanidis C, Galazios G, Koutsougeras G, Papadopoulos N, Lambropoulou M, Simopoulos C. · Department of Obstetrics & Gynecology, Democritus University of Thrace, Greece. · Eur J Gynaecol Oncol. · Pubmed #19317265 No free full text.

Abstract: BACKGROUND: Frozen section biopsy has been widely used for intraoperative diagnosis and evaluation of sentinel lymph nodes, so a decision can be made regarding whether to perform axillary clearance during primary surgery. This study aims to discuss the reliability of a simpler and faster method - touch imprint cytology - in the interpretation of metastasis from breast cancer. METHODS: A retrospective review of 41 sentinel lymph node biopsies from patients with breast cancer were examined by intraoperative imprint cytology using rapid Diff-Quick staining. Paraffin-embedded permanent sections were examined using hematoxylin and eosin stained sections from the sentinel lymph nodes in collaboration with the employment of an anti-cytokeratin antibody. RESULTS: Sixteen of all sentinel nodes harbored metastases in the paraffin sections, of which all 16 were identified by imprint cytology (sensitivity 93%). CONCLUSION: Touch imprint cytology is a fast and reliable alternative for intraoperative evaluation of sentinel lymph nodes in breast cancer patients.

Leary RJ, Lin JC, Cummins J, Boca S, Wood LD, Parsons DW, Jones S, Sjöblom T, Park BH, Parsons R, Willis J, Dawson D, Willson JK, Nikolskaya T, Nikolsky Y, Kopelovich L, Papadopoulos N, Pennacchio LA, Wang TL, Markowitz SD, Parmigiani G, Kinzler KW, Vogelstein B, Velculescu VE. · The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA. · Proc Natl Acad Sci U S A. · Pubmed #18852474 links to  free full text

Abstract: We have performed a genome-wide analysis of copy number changes in breast and colorectal tumors using approaches that can reliably detect homozygous deletions and amplifications. We found that the number of genes altered by major copy number changes, deletion of all copies or amplification to at least 12 copies per cell, averaged 17 per tumor. We have integrated these data with previous mutation analyses of the Reference Sequence genes in these same tumor types and have identified genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations included those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that could prove useful for cancer diagnosis and therapy.

Tamiolakis D, Tsamis I, Thomaidis V, Lambropoulou M, Alexiadis G, Venizelos I, Jivanakis T, Papadopoulos N. · Department of Cytology, General Hospital of Chania, Crete, Greece. · Chirurgia (Bucur). · Pubmed #17966942 No free full text.

Abstract: Jaw bone disorders causing oral complaints are common in primary care settings. Most of these conditions are of a chronic and benign nature. However they also may be the symptoms of a primary or secondary malignant process in the bone. The most common malignant bone tumor is metastatic carcinoma, and tumors arising in the breast, prostate, thyroid, lung and kidney have a special propensity to spread to bone. Yet metastases to the bones are rare; less than one per cent of all neoplasms metastases to the maxillofacial area. We describe four cases of metastatic tumours to the jaws. Two cases originated from the thyroid gland while the rest were from the oesophagus and the liver respectively. Three lesions occurred in the mandible and one in the maxilla. Patients presented with oral discomforts disregarding the primary tumor. Physicians who frequently advise patients with oral complaints should keep in mind that whereas these symptoms are mostly of a chronic and benign nature, metastases from a malignant tumor must be included in the differential diagnosis.

Wood LD, Parsons DW, Jones S, Lin J, Sjöblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, Silliman N, Szabo S, Dezso Z, Ustyanksky V, Nikolskaya T, Nikolsky Y, Karchin R, Wilson PA, Kaminker JS, Zhang Z, Croshaw R, Willis J, Dawson D, Shipitsin M, Willson JK, Sukumar S, Polyak K, Park BH, Pethiyagoda CL, Pant PV, Ballinger DG, Sparks AB, Hartigan J, Smith DR, Suh E, Papadopoulos N, Buckhaults P, Markowitz SD, Parmigiani G, Kinzler KW, Velculescu VE, Vogelstein B. · Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA. · Science. · Pubmed #17932254 links to  free full text

Abstract: Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.

Lin J, Gan CM, Zhang X, Jones S, Sjöblom T, Wood LD, Parsons DW, Papadopoulos N, Kinzler KW, Vogelstein B, Parmigiani G, Velculescu VE. · Ludwig Center for Cancer Genetics and Therapeutics, and The Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland 21231, USA. · Genome Res. · Pubmed #17693572 links to  free full text

Abstract: A recent study of a large number of genes in a panel of breast and colorectal cancers identified somatic mutations in 1149 genes. To identify potential biological processes affected by these genes, we examined their putative roles based on sequence similarity, membership in known functional groups and pathways, and predicted interactions with other proteins. These analyses identified functional groups and pathways that were enriched for mutated genes in both tumor types. Additionally, the results pointed to differences in molecular mechanisms that underlie breast and colorectal cancers, including various intracellular signaling and metabolic pathways. These studies provide a multidimensional framework to guide further research and help identify cellular processes critical for malignant progression and therapeutic intervention.

Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. · Ludwig Center and Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA. · Science. · Pubmed #16959974 links to  free full text

Abstract: The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers in unprecedented detail. To begin a systematic analysis of such alterations, we determined the sequence of well-annotated human protein-coding genes in two common tumor types. Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average of approximately 90 mutant genes but that only a subset of these contribute to the neoplastic process. Using stringent criteria to delineate this subset, we identified 189 genes (average of 11 per tumor) that were mutated at significant frequency. The vast majority of these genes were not known to be genetically altered in tumors and are predicted to affect a wide range of cellular functions, including transcription, adhesion, and invasion. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.

Tamiolakisl D, Venizelos I, Lambropoulou M, Jivannakis T, Seliniotakis E, Tsikouras P, Limberis V, Tsalkidis A, Papadopoulos N. · Department of Cytology, General Hospital of Chania. · Acta Medica (Hradec Kralove). · Pubmed #15844251 No free full text.

Abstract: AIM: Breast cancer is a frequent cause of death among women with gynaecologic malignancies despite the introduction of combination chemotherapy. There is therefore a need for new therapeutic strategies for patients with breast cancer, such as cellular immunotherapy. In this immunohistochemical study we analyzed the epithelial expression of major histocompatibility complex (MHC) class II (HLA-DR) on atypical and malignant primary mammary epithelial cells, as well as the magnitude of the stromal T lymphocytes (T4 subset) at the tumor site. EXPERIMENTAL DESIGN: The study was carried out retrospectively in tumor tissue from 82 patients with mammary lesions (31 cases of atypical ductal hyperplasia -ADH-, 12 cases of ductal carcinoma in situ -DCIS- and 39 cases of infiltrating ductal carcinoma not otherwise specified -IDC-NOS). Medullary carcinomas were not included in our investigation. Material used had been formalin fixed and paraffin embedded. RESULTS: HLA class II (DR) was expressed in 20 of 31 ADHs (64.5%), in 4 of 12 DCISs (33.3%), and in 10 of 39 IDC-NOSs (25.6%). CD4 was expressed in 9 of 31 ADHs (29%), in 5 of 12 DCISs (42%), and in 26 of 39 IDC-NOSs (67%). CONCLUSIONS: The results showed decreased epithelial expression of HLA class II (DR) and increased stromal expression of CD4, as the lesion progressed to malignancy. Gradual loss of epithelial HLA class II expression might be a manifestation of cellular differentiation from the atypical form versus the malignant one, signaling simultaneously a selective effect on the response capacity of the immune system.

Kakagia D, Trichas M, Papadopoulos N, Tsalkidis A, Jivannakis T, Tamiolakis D. · Department of Surgery, Democritus University of Thrace, Alexandroupolis, Greece. · Eur J Gynaecol Oncol. · Pubmed #15597849 No free full text.

Abstract: AIM: In the literature there are numerous large prospective studies on patients with locally advanced breast cancer, however little is reported on the management of ulcerative breast cancer. The aim of this study was to evaluate the employment of combined anthracycline-based chemotherapy and hormonal therapy in ulcerative locally advanced mammary carcinoma. PATIENTS AND METHODS: Four patients, aged from 67 to 83 years, presented with ulcerative breast cancer resulting in breast destruction. Histological examination of biopsy specimens revealed highly differentiated estrogen receptor-positive ductal carcinomas. All tumours were classified as locally advanced since there was no clinical or radiologic evidence of distant metastasis in any of the patients. Due to their religious beliefs all patients refused any other treatment but chemotherapy. In these patients hemostasis and reduction of bacterial overgrowth were followed by administration of anthracycline-based chemotherapy and hormonal therapy. RESULTS: All patients responded well; ulcer healing and partial remission were achieved for a period ranging from 19 to 28 months before disease progression. CONCLUSION: There is clinical evidence from this study that the combination of anthracycline-based palliative chemotherapy coupled with tamoxifen is beneficial for patients with inoperable ulcerative breast cancer.

Tamiolakis D, Venizelos D, Antoniou C, Tsiminikakis N, Alifieris E, Papadopoulos N. · Department of Cytology, General Hospital of Chania, Crete, Greece. · Onkologie. · Pubmed #15591718 No free full text.

Abstract: BACKGROUND: Poland's syndrome, a rare congenital anomaly characterized by a defect of the pectoralis muscles, has been reported in association with lymphoreticular malignancies and some solid tumors. CASE REPORT: We report the case of a 53-year-old woman with Poland's syndrome who developed breast cancer in the afflicted ipsilateral hypoplastic breast. FNA cytology revealed a moderately differentiated carcinoma and histology was consistent with a well differentiated invasive ductal carcinoma. CONCLUSION: Poland's syndrome can be associated with breast cancer so all females with the syndrome should be thoroughly examined for early detection of neoplasia.

Tamiolakis D, Venizelos I, Nikolaidou S, Prassopoulos P, Alexiadis G, Simopoulos C, Papadopoulos N. · Department of Cytology, General Hospital of Chania, Crete, Greece. · Onkologie. · Pubmed #15585977 No free full text.

Abstract: BACKGROUND: Rhabdomyosarcoma accounts for approximately 4% of all childhood malignancies. Breast metastases from rhabdomyosarcoma are uncommon with an incidence of 6%. CASE REPORT: We present a patient who developed bilateral mammary metastases from rhabdomyosarcoma arising in the right lower extremity. An 11-year-old female with a 20-month history of rhabdomyosarcoma was referred to our department because of bilateral breast enlargement. A needle core biopsy was performed and touch imprint slides were obtained. Cytology determined the masses to be metastases of rhabdomyosarcoma. MyoD1 immunostain and RT-PCR analysis confirmed the diagnosis. CONCLUSIONS: Cytomorphology with ancillary methods is essential in the diagnosis of metastatic breast deposits in order to avoid unnecessary mastectomy and to employ systemic treatment.

Krop I, Player A, Tablante A, Taylor-Parker M, Lahti-Domenici J, Fukuoka J, Batra SK, Papadopoulos N, Richards WG, Sugarbaker DJ, Wright RL, Shim J, Stamey TA, Sellers WR, Loda M, Meyerson M, Hruban R, Jen J, Polyak K. · Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, D740C, Boston, MA 02115, USA. · Mol Cancer Res. · Pubmed #15383627 links to  free full text

Abstract: HIN-1 (high in normal-1) is a candidate tumor suppressor identified as a gene silenced by methylation in the majority of breast carcinomas. HIN-1 is highly expressed in the mammary gland, trachea, lung, prostate, pancreas, and salivary gland, and in the lung, its expression is primarily restricted to bronchial epithelial cells. In this report, we show that, correlating with the secretory nature of HIN-1, high levels of HIN-1 protein are detected in bronchial lavage, saliva, plasma, and serum. To determine if, similar to breast carcinomas, HIN-1 is also silenced in tumors originating from other organs with high HIN-1 expression, we analyzed its expression and promoter methylation status in lung, prostate, and pancreatic carcinomas. Nearly all prostate and a significant fraction of lung and pancreatic carcinomas showed HIN-1 hypermethylation, and the majority of lung and prostate tumors lacked HIN-1 expression. In lung carcinomas, the degree of HIN-1 methylation differed among tumor subtypes (P = 0.02), with the highest level of HIN-1 methylation observed in squamous cell carcinomas and the lowest in small cell lung cancer. In lung adenocarcinomas, the expression of HIN-1 correlated with cellular differentiation status. Hypermethylation of the HIN-1 promoter was also frequently observed in normal tissue adjacent to tumors but not in normal tissue from noncancer patients, implying that HIN-1 promoter methylation may be a marker of premalignant changes. Thus, silencing of HIN-1 expression and methylation of its promoter occurs in multiple human cancer types, suggesting that elimination of HIN-1 function may contribute to several forms of epithelial tumorigenesis.

Tamiolakis D, Venizelos J, Prassopoulos P, Simopoulos S, Bolioti S, Tsiapali M, Papadopoulos N. · Department of Cytology, Democritus University of Thrace, Greece. · Onkologie. · Pubmed #15007251 No free full text.

Abstract: BACKGROUND: Extramedullary hematopoiesis (EMH) is associated with a number of diseases in which the normal function of the bone marrow is disturbed. While organs with hemopoietic capacity like the liver and spleen are most commonly involved, EMH has also occasionally been found in other organs like the adrenal gland, lymph nodes, breast, thymus, small bowel and central nervous system. However, presentation of a myeloproliferative disorder, such as EMH in these organs is a rare event. CASE REPORT: We report clinical and fine-needle aspiration (FNA) findings in a patient who presented with intrahepatic EMH which mimicked metastatic carcinoma from a colonic primary. RESULTS: Ultrasound-guided FNA of the intrahepatic mass revealed megakaryocytes and myelocytes thus establishing the diagnosis of EMH. CONCLUSIONS: EMH is an unusual condition that can mimic other solid masses of the liver. Because radiologic findings are not specific, EMH should be considered in the differential diagnosis, especially in patients with a myeloproliferative disorder. FNA and subsequent cytopathological interpretation of the aspirates enables avoidance of unnecessary potentially hazardous surgery.

Tamiolakis D, Papadopoulos N, Cheva A, Lambropoulou M, Kotini A, Jivannakis T, Simopoulos C. · Department of Cytology, Regional Hospital of Alexandroupolis, Greece. · Eur J Gynaecol Oncol. · Pubmed #12440829 No free full text.

Abstract: Myoepithelial cells are normally located between the epithelial cells and the basal lamina of secretory elements of exocrine glands. Their role in the histogenesis of breast tumours has been studied extensively, and a definite differentiation towards myoepithelial cells has been demonstrated in adenoid cystic carcinoma, adenomyoepithelioma, low-grade adenosquamous (syringomatous) carcinoma, pure malignant myoepithelioma and poorly differentiated myoepithelial-rich breast carcinoma. All these tumours are of low malignancy, with the exception of malignant myoepithelioma and poorly differentiated myoepithelial-rich carcinoma. We examined the possibility that invasive ductal carcinoma of the breast might show differentiation towards both epithelial and myoepithelial cells because there is no reason to assume that one type of differentiation necessarily excludes the other. We performed the avidin-biotin immunohistochemical analysis of 20 cases of infiltrating ductal carcinomas (IDCs) with diffuse fibrosis, 20 cases of IDCs without fibrosis and five cases of metaplastic carcinomas, to detect myoepithelial differentiation of the tumour cells. Myoepithelial differentiation was determined by the expression of alpha-smooth muscle actin (alpha-SMA). We concluded that IDCs with diffuse fibrosis are associated with a myoepithelial immunophenotype of carcinoma cells.

Tamiolakis D, Simopoulos C, Cheva A, Lambropoulou M, Kotini A, Jivannakis T, Papadopoulos N. · Department of Cytology, Regional Hospital of Alexandroupolis, Democritus University of Thrace, Greece. · Eur J Gynaecol Oncol. · Pubmed #12440819 No free full text.

Abstract: Medullary carcinoma (MC) of the breast is considered to carry a more favorable prognosis than other subtypes of infiltrating ductal carcinoma. This is a biological paradox because its clinical behavior contrasts with its anaplastic morphology. MC is characterized by a dense lymphocytic infiltrate. In this study, we determined the immunological profile of tumor infiltrating lymphocytes (TILs) in MC by CD20 (L26), CD8, and CD45RO (UCHL 1) immunostaining on paraffin-embedded sections. We examined 14 cases of typical MC (TMC), 15 cases of atypical MC (AMC) classified according to Ridolfi criteria (1977) and 19 cases of poorly differentiated infiltrating ductal carcinoma (PDC-NOS). TILs were quantified separately into cells infiltrating tumor nests (intraepithelial) and cells infiltrating tumor stroma (stromal). The number of CD8 positive and CD20 positive cells infiltrating tumor nests and tumor stroma were significantly increased in TMC and AMC as opposed to the PDC-NOS group. There was a loss in the number of CD45RO positive cells, both intraepithelial and stromal, in TMC and AMC as opposed to the PDC-NOS group. We conclude that MC tumor lymphocytic infiltrate demonstrates a mixed-T cytotoxic (CD8+) and B cell (CD20+)-immunophenotypic profile. This might in part explain the improved clinical outcome of the disease.

Papadopoulos N, Kotini A, Cheva A, Jivannakis T, Lambropoulou M, Bobos M, Vavetsis S, Tamiolakis D. · Department of Histology-Embryology, Democritus University of Thrace, Alexandroupolis, Greece. · Eur J Gynaecol Oncol. · Pubmed #12440813 No free full text.

Abstract: Vimentin is an intermediate filament protein normally expressed in mesenchymal cells, but evidence is accumulating in the literature which suggests that the aberrant expression of vimentin in epithelial cancer cells might be related to local invasiveness and metastatic potential. Previous studies strongly support the implication of vimentin in the metastatic progression of breast and cervical lesions. The secretory component is isolated from human colostrum and is of help in more precise grading of endometrial carcinoma. In this study we examined vimentin and secretory component (SC) expression in adenomatous hyperplasia, atypical adenomatous hyperplasia and well-differentiated adenocarcinoma (cribriform pattern). The results showed decreased expression of vimentin and increased expression of the secretory component as the lesion progressed to malignancy.

Papadopoulos N, Tamiolakis D, Lambropoulou M, Alexiadis G, Manavis J, Anastasiadis P, Sivridis E. · Department of Pathology, Democritus University of Thrace, Dragana-Alexandroupolis, Greece. · Eur J Gynaecol Oncol. · Pubmed #11446482 No free full text.

Abstract: Mammary non-Hodgkin's lymphomas are uncommon and account for 2% of all extranodal lymphomas. Stringent diagnostic criteria are applied in the diagnosis of primary lymphoma considering that the breast is a recognized site for disseminated extranodal lymphoma. Our case report was established by histology alone.

Papadopoulos N, Tamiolakis D, Lambropoulou M, Alexiadis G, Deftereos S, Manavis J, Polychronidis A, Sivridis E. · Department of Pathology, Democritus University of Thrace, Alexandroupolis, Greece. · Eur J Gynaecol Oncol. · Pubmed #11446477 No free full text.

Abstract: A case of mucinous carcinoma of the breast is reported in a female aged 71 years. On gross examination of the left mastectomy specimen two relatively well-circumscribed masses with a gelatinous cut surface were found. Touch imprint cytology was consistent with a low-grade malignancy and histologic and histochemical examination revealed a mucinous carcinoma. Careful prospective correlation between the cytological appearances of cells in imprints and the subsequent histopathology may lead to a more precise cytodiagnosis of a tumor associated with a comparative good prognosis.

Tamiolakis D, Papadopoulos N, Venizelos J, Lambropoulou M, Romanidis C, Petrakis G, Limberis V, Galazios G, Koutsougeras G, Simopoulos C. · Department of Cytology, Regional Hospital of Chania, Greece. · Onkologie. · Pubmed #16974114 No free full text.

Abstract: BACKGROUND: Imprint cytology may provide a fast and accurate method for intraoperative screening of sentinel lymph nodes, so a decision can be made regarding whether to perform axillary clearance during primary surgery. If the findings are negative, in many cases axillary dissection can be omitted. Patients and METHODS: 128 sentinel nodes from a cohort of 87 patients that had been identified using technetium-99m nanocolloid as a radioactive tracer and Patent blue dye were dissected for rapid Diff-Quick stained touch preparations. Intraoperative evaluation of sentinel node status by imprint cytology was correlated with histopathological results of permanent sections. Tumor-negative nodes in routine paraffin sections were further investigated with the employment of an anti-cytokeratin antibody. RESULTS: 36 of all sentinel nodes harbored metastases in the paraffin sections, of which 32 were identified by imprint cytology (sensitivity 88.8%). 3 sentinel nodes were positive by imprint cytology and negative by histopathology of the paraffin sections. Comparison of the results of the touch preparations with the final histopathology (hematoxylin-eosin and anticytokeratin antibody stains) demonstrated a sensitivity of 83.3% and a negative predictive value of 92.5%. The specificity and positive predictive value were 100% each. CONCLUSIONS: Touch imprint cytology is potentially useful for intraoperative evaluation of sentinel lymph nodes in breast cancer patients.