Vassiliki Malamou-Mitsi

Differential Response of Immunohistochemically Defined Breast Cancer Subtypes to Anthracycline-Based Adjuvant Chemotherapy with or without Paclitaxel

Background The aim of the present study was to investigate the efficacy of adjuvant dose-dense sequential chemotherapy with epirubicin, paclitaxel, and CMF in subgroups of patients with high-risk operable breast cancer, according to tumor subtypes defined by immunohistochemistry (IHC). Materials and Methods Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 1,039 patients participating in two adjuvant dose-dense sequential chemotherapy phase III trials were centrally assessed in tissue micro-arrays by IHC for 6 biological markers, that is, estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, cytokeratin 5 (CK5), and EGFR. The majority of the cases were further evaluated for HER2 amplification by FISH. Patients were classified as: luminal A (ER/PgR-positive, HER2-negative, Ki67low); luminal B (ER/PgR-positive, HER2-negative, Ki67high); luminal-HER2 (ER/PgR-positive, HER2-positive); HER2-enriched (ER-negative, PgR-negative, HER2-positive); triple-negative (TNBC) (ER-negative, PgR-negative, HER2-negative); and basal core phenotype (BCP) (TNBC, CK5-positive and/or EGFR-positive). Results After a median follow-up time of 105.4 months the 5-year disease-free survival (DFS) and overall survival (OS) rates were 73.1% and 86.1%, respectively. Among patients with HER2-enriched tumors there was a significant benefit in both DFS and OS (log-rank test; p = 0.021 and p = 0.006, respectively) for those treated with paclitaxel. The subtype classification was found to be of both predictive and prognostic value. Setting luminal A as the referent category, the adjusted for prognostic factors HR for relapse for patients with TNBC was 1.91 (95% CI: 1.31–2.80, Walds p = 0.001) and for death 2.53 (95% CI: 1.62–3.60, p<0.001). Site of and time to first relapse differed according to subtype. Locoregional relapses and brain metastases were more frequent in patients with TNBC, while liver metastases were more often seen in patients with HER2-enriched tumors. Conclusions Triple-negative phenotype is of adverse prognostic value for DFS and OS in patients treated with adjuvant dose-dense sequential chemotherapy. In the pre-trastuzumab era, the HER2-enriched subtype predicts favorable outcome following paclitaxel-containing treatment.

The value of neuroendocrine markers in non-small cell lung cancer: a comparative immunohistopathologic study

In order to estimate the value of immunohistochemical identification of neuroendocrine (NE) differentiation markers in non-small cell lung carcinomas (NSCLCs), we investigated the expression of five neuroendocrine and neural differentiation-related antigens in 51 NSCLCs. Additionally, 20 epithelial lung tumors with NE differentiation [15 carcinoids and five small cell lung carcinomas (SCLCs)] and 61 epithelial tumors of various other origin (breast, prostate, colon and head-neck carcinomas) were studied. An indirect two-stage immunoperoxidase method was performed in formalin-fixed and paraffin-embedded tissue specimens, by using commercially available monoclonal antibodies. These antibodies are directed against neuron-specific enolase (NSE), chromogranin-A and Leu-7 which are general markers of NE differentiation, bombesin, which is a specific NE secretory product and neurofilament triplet protein (NFTP), an intermediate filament protein of neuronal differentiation. All five markers demonstrated a positive immunoreactivity in NSCLCs, equally distributed to all three histologic subtypes, ranging from 16 to 47% of the cases (NSE 47%, bombesin 21.5%, Leu-7 21.5%, chromogranin-A 18% and NFTP 16%). Most of the carcinoids and SCLCs expressed multiple or all NE markers. The other four epithelial tumors showed a positive immunoreactivity for bombesin, Leu-7 and NFTP, ranging from 11 to 40% of the cases. Chromogranin-A was not expressed in any of these tumors, whereas NSE was demonstrated only in 17% of breast carcinomas. The following remarks can be drawn from this study: (1) some NSCLCs showed immunophenotypic NE differentiation; (2) among all the markers used, NSE was the most sensitive (sensitivity, 100%) and chromogranin-A the most specific (specificity, 100%); and (3) NSE and chromogranin-A appear to be the most valuable and useful indicators of probable neuroendocrine differentiation in lung epithelial tumors.

The shape and the thickness of the anterior cruciate ligament along its length in relation to the posterior cruciate ligament: a cadaveric study.

PURPOSE The purpose of this study was to evaluate the shape of the native anterior cruciate ligament (ACL) along its length in relation to the posterior cruciate ligament (PCL) and compare it with the size of the 3 commonly used autografts (bone-patellar tendon-bone [BPTB], single-bundle hamstring, and double-bundle hamstring). METHODS With the knee in extension, we filled the intercondylar notch with paraffin, fixing the cruciate ligaments in their natural position, in 8 cadaveric specimens. The ACL-PCL tissue specimen, embedded in paraffin, was removed en bloc. Gross sections were prepared in the coronal plane and were evaluated histologically. The width, thickness, and cross-sectional area of both the ACL and PCL were determined. The dimensions of the semitendinosus tendon (ST), gracilis tendon (GT), and BPTB grafts were measured and compared with those of the native ACL. RESULTS The PCL occupies the largest part of the intercondylar area, leaving only a small space for the ACL in knee extension. The ACL midsubstance has a width of 5 mm, resembling a band shape. Only before its tibial insertion does the ACL fan out and take the form of its tibial attachment. The BPTB graft has a thickness of 5.8 mm, whereas the ST and GT grafts have a thickness of 6.25 mm and 4.5 mm, respectively, and are comparable to the midsubstance of the ACL but undersized in the tibial insertion (P = .0016 for BPTB graft, P = .002 for ST graft, and P = .0003 for GT graft). A quadruple-looped ST-GT graft, with a diameter of 8 mm, is oversized in the midsubstance (P = .0002) but fits better in the tibial attachment. CONCLUSIONS The ACL midsubstance has a width of 5 mm, resembling a band shape. Before its tibial insertion, the ACL fans out like a trumpet, taking the form of its wide tibial attachment. CLINICAL RELEVANCE The dimensions of the native ACL have to be considered in graft selection for anatomic ACL reconstruction.

Sudden Death Due to an Unrecognized Cardiac Hydatid Cyst

Echinococcosis is an endemic disease, most common in sheep-raising communities, usually caused by the larval or cyst stage of the tapeworm Echinococcus granulosus. Isolated cardiac hydatid cyst is uncommon at any age, occurs through the coronary circulation, and accounts for less than 3% of all hydatid disease. We describe a case of an 1%-year-old female, who died suddenly. The post-mortem examination revealed an isolated cyst in the left ventricle of the heart with intact wall. The cytologic examination of the cyst fluid demonstrated the presence of the characteristic scolices and hooklets and established the diagnosis of cardiac hydatid cyst. The present case is of special interest because of the rare primary localization and the onset of sudden death in a young person as the initial manifestation of the disease.

Influence of glioma's multidrug resistance phenotype on (99m)Tc-tetrofosmin uptake.

PurposeMultidrug resistance (MDR) remains a major obstacle to successful chemotherapeutic treatment of cancer. Several chemotherapeutic and radiopharmaceutical agents are substrates of the pumps encoded by the MDR genes, and therefore, their accumulation is prevented. We evaluated in vivo whether [99mTc]tetrofosmin (99mTc-TF) uptake is influenced by the MDR profile of gliomas.ProceduresEighteen patients with histologically confirmed glioma were included in the study. Brain single-photon emission computed tomography by 99mTc-TF was performed within a week prior to surgical excision, and the expression of MRP5 was assessed by immunohistochemistry. Radiotracer accumulation was assessed by a semiquantitative method, calculating the lesion-to-normal uptake ratio.ResultsUsing Spearmans ρ analysis, we found no correlation between tracer uptake expressed as lesion-to-normal and MRP5 expression. There was a significant correlation between glioma aggressiveness as assessed by Ki-67/MIB-1 and MRP5 expression.ConclusionThe present data suggest that 99mTc-TF uptake is not influenced by gliomas MDR phenotype. Thus, 99mTc-TF constitutes a suitable radiotracer for imaging gliomas.

Targeting c-KIT, PDGFR in cancer of unknown primary: a screening study for molecular markers of benefit

AimsIn view of available targeted therapies, we investigated the presence of c-kit, PDGFR gene mutations and protein expression in cancer of unknown primary (CUP) in order to study their contribution in pathogenesis, their prognostic value and potential as therapeutic targets.MethodsMutations in hot spots c-kit exon 11 and PDGFR exons 12 and 18 were studied in paraffin-embedded tumour samples from 50 patients with CUP by means of PCR-based single-strand conformational polymorphism and protein expression by means of streptavidin-biotin immunoperoxidase assays. Molecular markers were screened for possible correlations with patient outcome.ResultsNo shifted band was detected in any of the polyacrylamide gel electrophoreses, indicating absence of c-kit exon 11 and PDGFR exon 12, 18 mutations. Immunohistochemical analysis in 37 tumours revealed positive membranous CD117 expression in 30 samples (81%) of which five exhibited strong (+3), four moderate (+2) and 21 weak (+1) staining. PDGFRa protein staining was seen in 15 out of 30 (50%) cases, mostly weak (13) and rarely moderate (1) or strong (1). The expression of KIT or PDGFRa protein did not correlate with the clinical outcome of the patients in our cohort.ConclusionsIn a moderate-sized CUP patient cohort, KIT or PDGFRa protein overexpression is rare, does not have gross prognostic significance for survival and is not associated with presence of activating mutations.

Subcutaneous Metastasis of Peritoneal Mesothelioma Diagnosed by Fine-Needle Aspiration

Mesothelioma is a rare malignant neoplasm of the serosal membranes, which can give distant metastases in various organs in advanced stages of its course. Subcutaneous tissue is an unusual metastatic site. In the literature, only one case of metastatic mesothelioma to the skin of the face has been reported. We present a case of a 60-year-old female with a prior history of peritoneal malignant mesothelioma, who 6 months after the initial diagnosis presented with a subcutaneous nodule in the lateral chest wall. Cytological examination of the material obtained by FNA from the nodule revealed metastatic mesothelioma. Although subcutaneous metastasis of malignant mesothelioma is a rare entity, one must always keep this possibility in mind and proceed to further investigation of such lesions. In these cases, FNA is a simple diagnostic procedure for the identification of metastatic disease in patients with a prior history of malignancy.

Histologic comparison of vibrating guidewire with conventional guidewire technique in an experimental coronary in vivo model.

AbstractPurpose: To compare the damage caused by vibrating guidewire manipulation and conventional guidewire manipulation of soft coronary wires in normal sheep coronary arteries. Methods: Using an intact sheep model the two methods of passing a coronary guidewire down a normal coronary artery under fluoroscopic screening control were studied. The resulting arterial damage caused by the two techniques was studied histologically. The severity of damage was scored from 1 (no damage) to 4 (severe damage) and expressed as: (a) percentage of damaged sections, (b) mean damage score per section and (c) percentage of sections suffering the most severe degree of damage (scores 3 and 4). Results: One hundred and sixty-eight sections were studied. The percentage of damaged sections was lower in the vibrating guidewire group (p = 0.004). The mean damage score and the percentage of sections with a damage score of 3 or 4 were smaller in the vibrating guidewire group than in the conventional guidewire manipulation group (p = 0.001 and p = 0.009, respectively). Conclusions: Both methods of guidewire manipulation cause identifiable vascular damage. The extent and severity of damage appear greater when the guidewire is manipulated manually.

Contribution of Exfoliative Cytology to the Diagnosis of Laryngeal Lesions

OBJECTIVE To estimate the diagnostic accuracy and reliability of exfoliative laryngeal cytology. STUDY DESIGN Over three years (1996-1999) cytologic smears were obtained from clinically suspicious laryngeal lesions during laryngoscopy in a total of 31 selected patients (28 males and 3 females with an age range from 28-90 years). The cytologic diagnoses were analyzed and correlated with the histologic and final clinical diagnoses in 17 and 14 cases, respectively. Cytologic identification of the exact histologic type of the lesion was evaluated in 17 patients from whom both cytologic smears and biopsy material were obtained. RESULTS The overall specificity was 100%, with no false positive diagnoses. The overall sensitivity was 93.3%, with one false negative cytologic diagnosis, in a case of non-Hodgkins lymphoma. Cytohistologic correlation showed complete agreement between cytologic and histologic diagnoses in five of six benign lesions, in four cases of dysplasia and in six cases of squamous cell carcinoma. The overall diagnostic accuracy of cytology was 96.7% CONCLUSION Exfoliative cytology by the smear technique is a reliable and accurate method in clinically suspected laryngeal lesions. Moreover, exfoliative cytology may be applied as the only alternative diagnostic method, especially in elderly patients with coexistent cardiorespiratory problems, when biopsy is not advisable or indicated.

The contribution of aqueous humor cytology in the differential diagnosis of anterior uvea inflammations

Background:Cytology of the aqueous humor can confirm the diagnosis of many intraocular conditions by revealing inflammatory cells, ghost red cells, lens material, and microorganisms. Purpose:The purpose of this study was to emphasize the contribution of aqueous humor fine needle aspiration cytology in cases where there is a clinical diagnostic dilemma whether an infectious or a noninfectious inflammatory process of the uvea is present. Methods:Collection of 0.15–0.2 ml aqueous humor was carried out with an insulin needle. The aspirated aqueous was then prepared for examination using either the Cytospin or the Thin-Prep technique and smears were stained with modified Papanikolaou and May-Grünwald-Giemsa stains. Results:Cytology of the aqueous humor essentially facilitated the differential diagnosis in 16 cases with an anterior uveal inflammation clinical picture. The cases included phacoanaphylactic endophthalmitis (n = 6), chronic postoperative bacterial endophthalmitis (n = 3), phacolytic glaucoma (n = 2), ghost cell glaucoma (n = 2), metastatic endophthalmitis (n = 1), post-traumatic lenticular abscess (n = 1), and iridocyclitis (n = 1). Treatment of the cases was successful. Conclusions:In selected cases, cytology of the aqueous humor reveals specific, with regard to the clinical entity, cell populations and other elements and thus contributes effectively to the differential diagnosis and therapeutic approach to some anterior uvea inflammations.