Preinvasive Cancer Research Articles

Automated Intra-Operative Analysis of Breast Cancer.

Abstract Background: Multiple operations are a major problem for breast conservation therapy. Accurate interpretation of intra-operative tumor margins can limit multiple re-excision procedures in order to obtain negative margins while maintaining a good cosmetic result from BCT. Intra-operative touch preparations have been used in the past but can be difficult to interpret without an experienced cytopathologist.Objective: To examine the reliability of fluorescently labeled intra-operative touch preps in conjunction with automated analysis in correctly identifying cancer cells compared to final pathologic diagnosis.Methods: Touch preps were propctively performed on 38 consecutive cases of patients undergoing breast surgery. The surgical cases included 15 invasive tumors, 9 ductal carcinoma in situ, 5 prophylactic mastectomies, and 9 normal tissues from breast reduction operations. Tumors were grossly located by a surgical pathologist and a cross sectional cut was made at the suspected tumor center. Touch preps with poly-l-lysine coated slides were then taken on the tissue surfaces exposed from the cross sectional cut. Additionally, the location where the touch preps were performed was isolated in a cassette and separated for later comparison. In cases of benign disease, touch preps were performed at the center of the excised tissue. The slides were fixed in 95% ethanol and stained with a Cytokeratin, an epithelial cell marker, and Hoechst, a nuclear stain. The prepared slides were then imaged with an automated fluorescent microscope, and suspected cancer cells were detected through standard image processing and statistical techniques.Results: The overall accuracy of our automated fluorescence analysis was 95% for identifying invasive or pre-invasive cancer compared final pathologic diagnosis. The overall specificity was 100% (there were no false positives). The sensitivity for ductal carcinoma in situ was 75% and invasive cancer was 90%. Overall sensitivity was 87% which is comparable to the best reported results from manual examination of touch preparations.Conclusion: Automated analysis of fluorescently stained touch prep slides is highly accurate in identifying cancer with no false positives. The immunofluorescence stains and automated microscopy may help the pathologist to quickly identify cancer cells in fresh breast tissue during BCT operations, and, thus, limit breast re-excisions in the future. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6016.

Prevalence of cervical intraepithelial neoplasia grades II/III and cervical cancer in patients with cytological diagnosis of atypical squamous cells when high-grade intraepithelial lesions (ASC-H) cannot be ruled out

The latest update of the Bethesda System divided the category of atypical squamous cells of undetermined significance (ASCUS) into ASC-US (undetermined significance) and ASC-H (high-grade intraepithelial lesion cannot be ruled out). The aims here were to measure the prevalence of pre-invasive lesions (cervical intraepithelial neoplasia, CIN II/III) and cervical cancer among patients referred to Instituto Fernandes Figueira (IFF) with ASC-H cytology, and compare them with ASC-US cases. Cross-sectional study with retrospective data collection, at the IFF Cervical Pathology outpatient clinic. ASCUS cases referred to IFF from November 1997 to September 2007 were reviewed according to the 2001 Bethesda System to reach cytological consensus. The resulting ASC-H and ASC-US cases, along with new cases, were analyzed relative to the outcome of interest. The histological diagnosis (or cytocolposcopic follow-up in cases without such diagnosis) was taken as the gold standard. The prevalence of CIN II/III in cases with ASC-H cytology was 19.29% (95% confidence interval, CI, 9.05-29.55%) and the risk of these lesions was greater among patients with ASC-H than with ASC-US cytology (prevalence ratio, PR, 10.42; 95% CI, 2.39-45.47; P = 0.0000764). Pre-invasive lesions were more frequently found in patients under 50 years of age with ASC-H cytology (PR, 2.67; 95% CI, 0.38-18.83); P = 0.2786998). There were no uterine cervical cancer cases. The prevalence of CIN II/III in patients with ASC-H cytology was significantly higher than with ASC-US, and division into ASC diagnostic subcategories had good capacity for discriminating the presence of pre-invasive lesions.

Epidermal Growth Factor Receptor Protein Expression and Gene Amplification in Normal, Hyperplastic, and Cancerous Glottic Tissue: Immunohistochemical and Fluorescent in Situ Hybridization Study on Tissue Microarrays

To evaluate the importance of epidermal growth factor receptor (EGFR) protein overexpression and gene amplification in carcinogenesis of glottic cancer. In order to evaluate EGFR expression at protein and gene level, immunohistochemical (IHC) analysis and fluorescent in situ hybridization (FISH) were performed on tissue microarrays of laryngeal tissue (145 samples) -- 38 samples of normal mucosa, 46 samples of hyperplastic lesions, and 61 samples of cancerous lesions. Membranous (mEGFR) and cytoplasmic (cEGFR) EGFR expression was significantly different between the analyzed groups. The differences were most striking in the suprabasal-transforming zone. IHC evaluation showed that high and low mEGFR staining contributed to the differentiation of dysplastic lesions, simple hyperplasia, and cancerous tissue, as well as between different degrees of atypia in hyperplastic lesions (P<0.050). EGFR gene amplification was not found in simple and abnormal hyperplastic lesions, but it was confirmed in 2/21 atypical hyperplasias, indicating that gene amplification can facilitate identification of malignant potential in hyperplastic lesions. In cancerous tissue, EGFR gene amplification was found in 8/50 samples. EGFR gene amplification was found in preinvasive cancer in one patient. In invasive carcinomas, gene amplification was not associated with stage or grade. Carcinomas with gene amplification showed significantly higher cEGFR expression (basal layer P=0.003; suprabasal layer P=0.002). This study confirmed an increase in EGFR protein expression and gene amplification with the increase in biological aggressiveness of glottic lesions. A correlation between EGFR gene amplification and protein expression was established. Gene amplification proved to be an early event in glottic carcinogenesis, indicating its importance for glottic cancer prevention, early detection, and protocol selection.

Another Duel in the Sun: Weighing the Balances Between Sun Protection, Tanning Beds, and Malignant Melanoma

The purpose of this report is to put the dueling factors of risk and prevention for melanoma in perspective for the thoughtful pediatric specialist to facilitate preteen preventive health counseling. We examined the rate of malignant melanoma among Kentucky residents and compared this rate with indicators of tanning bed prevalence in a large metropolitan area and sunscreen sales from a major distributor. We obtained malignant melanoma annual incidence data from the Kentucky Cancer Registry, which recorded Kentucky population incidence rates over the years 1995 to 2004. The rates reflected 2 malignant melanoma classifications: pre-invasive cancer only, or both invasive and noninvasive cancers combined. The age-adjusted incidence rate per hundred thousand for combined invasive and pre-invasive malignant melanoma swelled from 21.9 in 1995 to 31.3 in 2004. The respective invasive-only malignant melanoma incidence rates increased less dramatically, from 17.3 to 20.7, during this same 10-year time period. Since 1983, the number of separate tanning bed businesses increased from 1 in 1983 to 119 by the mid-1990s, and then declined to about 74 separate businesses by 2003. Sunscreen sales data is uneven between states and is currently inconclusive. Although current data cannot draw a precise link between melanoma and the use of tanning beds, the associated risk is implicit, as the ultraviolet A (UVA) and ultraviolet B (UVB) radiation in tanning bed usage is a well-established melanoma risk factor. In advising patients, the pediatric specialist should consider that melanoma rates are poised as a balance of some known risk factors and a few potential preventive factors.

The Mexican Cervical Cancer Screening Trial: Self-Sampling for Human Papillomavirus With Unaided Visual Inspection as a Secondary Screen

The Mexican Cervical Cancer Screening (MECCS) study took place in the State of Michoacán. Primary screening was by self-sampling for high-risk human papillomavirus (HR-HPV). The objectives were to increase the specificity of primary HPV screening by requiring 2 positive HPV tests 1 year apart in women whose secondary screen was negative according to an acetic acid-aided visual inspection (VIA). In addition, we postulated that the sensitivity of VIA would be sufficient to identify large preinvasive lesions and cancers unsuitable for cryotherapy if applied in a see-and-treat algorithm.A total of 8621 women (aged 30-50 years) were screened, and 14.3% were positive for HR-HPV. In phase 1, 11.9% of the HPV-positive women were VIA-positive and were referred for colposcopy with directed and random biopsies. If VIA-negative, women repeated the self-sample 1 year later to detect persistent HR-HPV (25.2% were positive). If persistently HR-HPV-positive in phase 2, patients again had VIA, then all women (both VIA-positive and -negative) received directed and random biopsies. If cryotherapy had been used to treat HPV- and VIA-positive women in phase 1 or persistent HR-HPV-positive (phase 2), the potential risk of undertreatment would have been 4.1%, and 66.4% of the treated patients would have had normal or cervical intraepithelial neoplasia I on biopsy. The VIA triage would refer 0.73% of the patients to colposcopy owing to the lesion size, location, or the presence of a cancer. On the basis of this pilot study, we are encouraged to explore and evaluate a rapid, more sensitive, and more specific self-test.

Triage value of high risk human papilloma virus detection in women with abnormal cervical cytology

To evaluate the triage value of high risk human papilloma virus (hrHPV) detection in the women with abnormal cervical cytology. 28,650 women underwent thinprep cell test (TCT) to screen cervical cancer. 694 of the 2433 patients with abnormal cervical cytology were randomly selected to undergo hrHPV HC II test to detect high risk HPV. 275 of these 694 patients received colposcopy and biopsy, 71, 149, and 55 of which were diagnosed as with atypical squamous cell (ASC), low squamous intraepithelial lesion (LSIL), and high squamous intraepithelial lesion (HSIL) respectively. The triage value of hrHPV detection was analyzed. Among the 694 patients, the incidence rates of hrHPV infection of those with ASC, LSIL, and HSIL were 68.4% (252/368), 87.6% (219/250), and 93.4% (71/76) respectively. Among the 275 cases who received colposcopy and biopsy the percentages of histopathologic lesion CIN2 in those with ASC, LSIL, and HSIL were 22.5%, 30.2%, and 70.9% respectively. When with CIN2 + as terminal, the sensitivity and specificity of hrHPV test were 93.8% and 23.6% in the ASC group; 93.1% and 10.6% in the LSIL group, and 97.4% and 25.0% in the HSIL group. Histopathologic lesions CIN3 or worse were seen in 7.0% of the patients with ASC, 12.2% of the patients with LSIL, and 36.4% of the patients with HSIL. When with CIN3 + as the terminal the sensitivity and specificity of hrHPV test were 100% and 21.2% in the ASC group; 100% and 10.7% in the LSIL group; and 95.0% and 11.4% in the HSIL group. hrHPV infection is associated with preinvasive cervical cancer and invasive cervical cancer. hrHPV test is a good triage approach for the patients with ASC, able to decrease about 50% of colposcopic referral. For the patients with LSIL and HSIL, hrHPV test is not an appreciate triage test and immediate colposcopy is recommended.

Magnetic Resonance Imaging of the Breast Improves Detection of Invasive Cancer, Preinvasive Cancer, and Premalignant Lesions during Surveillance of Women at High Risk for Breast Cancer

To assess the diagnostic accuracy of mammography, ultrasound, and magnetic resonance imaging (MRI) of the breast in the surveillance of women at high risk for breast cancer. In this prospective comparison study, women at high risk for breast cancer were offered annual surveillance examinations, consisting of mammography, ultrasound, and MRI, at a single tertiary care breast center. The sensitivity and specificity of each modality was based on the histopathologic evaluation of suspicious findings from all modalities plus the detected interval cancers. Three hundred and twenty-seven women underwent 672 complete imaging rounds. Of a total of 28 detected cancers, 14 were detected by mammography, 12 by ultrasound, and 24 by MRI, which resulted in sensitivities of 50%, 42.9%, and 85.7%, respectively (P < 0.01). MRI detected not only significantly more invasive but also significantly more preinvasive cancers (ductal carcinoma in situ). Mammography, ultrasound, and MRI led to 25, 26, and 101 false-positive findings, which resulted in specificities of 98%, 98%, and 92%, respectively (P < 0.05). Thirty-five (35%) of these false-positive findings were atypical ductal hyperplasias, lesions considered to be of premalignant character. Nine (26%) of those were detected by mammography, 2 (6%) with ultrasound, and 32 (91%) with MRI (P < 0.01). Our results show that MRI of the breast improves the detection of invasive cancers, preinvasive cancers, and premalignant lesions in a high-risk population and should therefore become an integral part of breast cancer surveillance in these patients.

Radiohybridization PET imaging of KRAS G12D mRNA expression in human pancreas cancer xenografts with [64Cu]DO3A-peptide nucleic acid-peptide nanoparticles

There is a compelling need to image pancreas cancer at an early stage. Human pancreas cancer cells display elevated levels of KRAS protein due to high copy numbers of KRAS mRNA, and elevated levels of insulin-like growth factor 1 receptor (IGF1R) due to overexpression of IGF1R mRNA. Therefore we hypothesized that pancreas cancer could be detected in vivo with a single probe that targets both KRAS mRNA and IGF1R. Because positron emission tomography (PET) is a sensitive imaging technique, we designed a probe incorporating the positron-emitting nuclide 64Cu. The KRAS-specific hybridization probe consisted of 1,4,7-tris(carboxymethylaza)cyclododecane-10-azaacetyl (DO3A) on the N-terminus of a peptide nucleic acid (PNA) hybridization sequence (GCCATCAGCTCC) linked to a cyclized IGF1 peptide analog (D-Cys-Ser-Lys-Cys) on the C-terminus, for IGF1R-mediated endocytosis. A series of such KRAS radiohybridization probes with 0, 1, 2, or 3 mismatches to KRAS G12D mRNA, including exact matches to wild type KRAS mRNA and KRAS G12V mRNA, along with a double D(Ala) replacement IGF1 peptide control, were assembled by continuous solid phase synthesis. To test the hypothesis that KRAS-IGF1 dual probes could specifically image KRAS mRNA expression noninvasively in human IGF1R-overexpressing AsPC1 pancreas cancer xenografts in immunocompromised mice, [64Cu]PNA radiohybridization probes and controls were administered by tail vein. The [64Cu]KRAS¬-IGF1 radiohybridization probe yielded strong tumor contrast in PET images, 8.6±1.4-fold more intense in the center of human pancreas cancer xenografts than in the contralateral muscle at 4 h post-injection. Control experiments with single base KRAS¬ mismatches, an IGF1 peptide mismatch, and a breast cancer xenograft lacking KRAS activation yielded weak tumor contrast images. These experiments are consistent with our hypothesis for noninvasive PET imaging of KRAS oncogene expression in pancreas cancer xenografts. Imaging oncogene mRNAs with radiolabel-PNA-peptide nanoparticles might provide specific genetic characterization of pre-invasive and invasive pancreas cancers for staging and choice of therapy.

Silent killer of the night: a feasibility study of an outreach well-women clinic for cervical cancer screening in female sex workers in Hong Kong

The purpose of this study was to see if an outreach model could be a feasible option for early detections of preinvasive cervical cancer in women with double identities of female sex workers (FSW) and illegal migrant workers in Hong Kong who most needed cervical screening but were often deprived of such a service. High turnover rates, acceptability, and compliance for follow-ups could potentially render such a clinical model unsuccessful. A total of 245 FSW were screened at the outreach clinic from January 2004 to December 2005, which was set up in a nongovernmental organization in a red light district. A questionnaire regarding their lifestyles and demographic details was used before a gynecological history, Papanicolaou (PAP) smear, and other health checkup were conducted. Chi-square test and multinomial logistic regression were used to analyze the results. Of 235 women tests, 9.8% of them had CIN I-III, and places of origin were found to be important risk factors for abnormal PAP smears. The nonlocal workers were significantly more likely to have abnormal PAP smears (chi(2)= 10.55, P= 0.04). Among the women, 88.1% of them who had the tests returned for follow-up with poorer compliance among those with an abnormal result. We conclude that an outreach well-women clinic seems to be an acceptable option for these women and an effective way for the early detection of cervical cancer.

Human Papillomavirus Infection in Malignant and Benign Gynaecological Conditions: A Study in Greek Women

HPV infection is by far the most frequent sexually transmitted disease. Our aim in this prospective nonrandomized study was to investigate the frequency with which different subtypes of the human papillomavirus (HPV) are found in gynaecological malignant and benign conditions and to compare the rate of infection between them. Detailed data of 195 women were selected and divided into three groups. The first group consisted of specimens from 68 women with cervical cancer. The second group consisted of specimens from 43 women with endometrial and ovarian cancer. The third group consisted of 84 specimens from women who were operated on for benign gynaecological diseases. Seven oncogenic types of HPV (6, 11 [low-risk subtypes] 16, 18, 31, 33, and 51 [high-risk subtypes]) were investigated by using the in situ hybridization technique. The HPV detection rate was higher in the cervical cancer group (74.8%), compared with the second (27.9%) and third (45.2%) groups. The most common HPV subtypes in the first group were 16 and 18. The most common subtypes in the second group were the 31, 33, and 51, and in the third group the 6 and 11 subtypes. Women developed cervical cancer at a younger age than endometrial or ovarian cancer. Smoking and exposure to multiple sexual partners appeared related to the development of cervical cancer. The use of contraceptive pill, dietary habits, and diabetes did not seem to increase the risk of HPV infection in this population. As it is common in other populations, in this selected population of Greek women we were able to confirm that in women with cervical cancer the most common HPV subtypes are 16 and 18. Education of adolescents on the epidemiological association of smoking and unprotected intercourse with cervical cancer will certainly help to reduce the rates of development of preinvasive and invasive cancer of the cervix in young women.

Detection of Pre-Invasive Lung Cancer: Technical Aspects of the LIFE Project

Lung cancer is the leading cause of cancer deaths in both men and women in the United States. The LIFE (Light Induced Fluorescence Endoscopy) Project was initiated at the University of North Carolina Medical Center in November, 1999, for the dual purposes of (1) detecting pre-invasive lung cancer in high-risk patients and (2) studying the molecular biology of pre-invasive lesions of the bronchus for possible development of molecular biomarkers. Of the 47 patients enrolled, all were current or former tobacco smokers, except for 1. Fluorescence endoscopy was utilized, in addition to white light bronchoscopy, to increase the detection of intraepithelial lesions. Adjacent biopsies were submitted for permanent and frozen sections, respectively, from four predetermined sites as well as from any abnormal areas. The snap-frozen specimens were cryostat sectioned, and the mucosal epithelial cells laser capture microdissected for DNA analysis. The great majority of specimens yielded sufficiently abundant and intact DNA to accomplish the molecular objectives. Histologic concordance of adjacent permanent and frozen sections was equivalent to the concordance of adjacent permanent sections, suggesting that frozen section diagnosis was adequate for the research purpose of correlating histology with molecular analysis.

Pre-invasive cervical disease and uterine cervical cancer in Brazilian adolescents: prevalence and related factors

The objective was to describe the prevalence and factors associated with uterine cervical cancer (CA) and high-grade squamous intraepithelial lesions (HSIL) in adolescents. A cross-sectional study was carried out with 702 sexually active adolescents treated at a general hospital in Rio de Janeiro, Brazil, from 1993 to 2002. Screening was performed by cytopathology and colposcopy and confirmation by biopsy. Exposure variables were socio-demographic characteristics and those related to reproductive health, habits, and sexual behavior. Adjusted odds ratios were estimated using multivariate logistic regression analysis. Based on histopathology, the prevalence of HSIL/CA was 3% (95%CI: 1.8-4.6). There was one case of invasive cancer. With each additional pregnancy, the odds of HSIL/CA increased by 2.2 (95%CI: 1.1-4.4). Age was also associated with this outcome, doubling the odds of acquiring this degree of disease with each year of age (OR = 2.0; 95%CI: 1.2-3.4). The prevalence of lesions suggests the importance of including sexually active adolescent females in cervical cancer screening programs aimed at early detection and treatment of these lesions.

Analysis of the VEGF family and their receptors in serum/plasma of patients with pre-invasive and invasive cervical cancer

5016 Background: The vascular endothelial growth factor (VEGF) family and their receptors are essential regulators of angiogenesis and lymphangiogenesis. This study examined the significance of circulating VEGF, VEGF-C, VEGF-D and their receptors VEGFR-1 and VEGFR-2 in patients with preinvasive and invasive cancer in relation to conventional prognostic parameters. Methods: Blood samples were obtained from 125 women before initial treatment (CIN I-III n = 50; FIGO stage I-IV n = 51; relapse n = 24). Plasma (p) and serum(s) levels of pVEGF, sVEGF-D, sVEGFR-1, sVEGFR-2 (R&amp;D Systems, USA) and sVEGF-C (IBL, Japan) were determined by using a quantitative sandwich enzyme-linked immunosorbent assay (ELISA). Results: The highest level of pVEGF (p = 0.007) and sVEGFR-2 (p = 0.014) were detected in patients with recurrent disease, whereas the highest level of sVEGF-D (p = 0.046) were measured in patients with preinvasive lesions (CIN I-III). Furthermore, significantly elevated levels of sVEGF-C (p = 0.021) were detected in early stages (FIGO I-II) in comparison with advanced stages (FIGO III-IV) of cervical cancer. No significant difference in concentration was observed between the various grades of cervical intraepithelial neoplasia (CIN I-III). Correlations between conventional prognostic markers such as lymph node status (N0/N1), lymphangioinvasion (L0/L1), angioinvasion (V0/V1) and grading (G1/G2/G3) were investigated. Increased plasma levels of VEGF (p = 0.036) correlate with the dissemination of tumor cells to regional lymph nodes (N1),whereas serum VEGF-D levels were significantly decreased in women with lymph-node involvement (N1) (p = 0.045) and vascular invasion (L1) (p = 0.019). None of these members of the VEGF family were found to correlate significantly with histological subtype (squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma) or grading of the tumor cells (G1/G2/G3). Conclusions: These results show that circulating concentrations of VEGF are associated with the stage of disease. In an early stage of cervical cancer a switch to a lymphangiogenic phenotype (VEGF-D, VEGF-C) might be possible. No significant financial relationships to disclose.

The inherited genetics of pancreatic cancer and prospects for secondary screening

It is estimated that pancreatic cancer has a familial component in approximately 5-10% of cases. Some of these cases are part of a defined cancer syndrome with a known gene mutation but in the remaining the causative gene remains unknown. In recent years, a better understanding of the molecular events that occur in the progression model of pancreatic cancer has lead to the development of secondary screening programmes with the aim of identifying early precursor lesions or pre-invasive cancer at a stage amenable to curative resection. High-risk groups who have an inherited predisposition for pancreatic cancer form the ideal group to study in developing a robust screening programme. Multimodality screening using computed tomography and endoluminal ultrasound in combination with molecular analysis of pancreatic juice are proving promising as diagnostics tools or at least serving as predictors of risk over a defined period.

Editor's Choice

Editor's Choice

P-054 Selection of pre-invasive and early invasive lung cancer binding peptides using random phage display libraries

P-054 Selection of pre-invasive and early invasive lung cancer binding peptides using random phage display libraries

E40. Genetic alterations in pre-invasive lung cancer

E40. Genetic alterations in pre-invasive lung cancer

Mamma-Sonographie mit 7,5 MHz versus 13 MHz: Ist eine Verbesserung der diagnostischen Sicherheit im Rahmen der komplementären Mammadiagnostik möglich?

Complementary diagnostic methods in early diagnosis of breast cancer are used to increase diagnostic accuracy and minimize unnecessary invasive diagnostic procedures. Aim of the following prospective, open multicenter clinical study was to define the value of high-frequency breast ultrasound with 13 MHZ transducers compared to standard breast ultrasound with 7.5 MHz. Data of 810 female patients, aged 45 to 60 years, with 819 suspicious breast lesions evaluated by four participating centres between October 1996 and December 1997. Standardised breast ultrasound was performed uniformly using a AU4 IDEA diagnostic ultrasound system by Esaote-Biomedica in addition to a standardised procedure of clinical examination and standard-2view-mammography. Analysis of all aquired data and the correlating histopathological findings was done by means of descriptive statistics on the basis of an access datafile (Version 2.0). The histopathological evaluation showed 435 benign and 384 malignant findings. Overall sensitivity and specificity of the clinical examination were 71.1 % and 88.9 % and for mammography 84.7 % and 76.5 %, respectively. Standard ultrasound with 7,5 MHz reached a sensitivity of 82,6 % and a specificity of 80.8 % high-frequency ultrasound with 13 MHz came to 87.2 % and 78.4 %, respectively. Regarding tumour size, mammography gave the highest sensitivity in detection of pre-invasive cancers (DCIS). High-frequency breast ultrasound (13 MHz) proved to have a higher diagnostic accuracy compared to standard breast ultrasound (7,5 MHz) regardless of tumour size. Sensitivity was especially improved in case of small invasive tumours (pT1a) with 78 % versus 56 %, respectively. We conclude that high-frequency ultrasound is a valueable additive tool especially in the diagnosis of small tumours, improving diagnostic safety and reducing unnecessary invasive diagnostic procedures.

Serum melatonin circadian profiles in women suffering from cervical cancer

Although there is an increasing evidence that the pineal gland may play a role in human malignancy, the studies on melatonin concentrations in different types of malignant tumors brought about controversial results. However, changes in melatonin concentrations have been observed in some types of human malignant tumors. Therefore, we decided to study the circadian melatonin rhythm in patients suffering from cervical cancer in different stages of progression and to compare them with those in subjects free from neoplastic disease. A total of 45 women were analyzed in this study. The subjects were divided into two groups. The first group consisted of 31 patients [mean age 52.1 +/- 1.8 yr (mean +/- S.E.M.), range 32-77 yr] with cervical cancer in various stages of the disease. The second group consisted of 14 healthy volunteers [mean age 53.5 +/- 2.0 yr (mean +/- S.E.M.), range 42-63] who served as the control group. Blood samples were collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00, and 08:00 hours. Melatonin concentration was measured by immunoenzymatic method. There were significant differences in circadian melatonin profiles as well as in the area under curve among the two studied groups. Melatonin concentrations were significantly lower in cancer patients in comparison with healthy individuals. Taking into consideration stage of the cervical cancer significantly lower melatonin secretion has been found in all subgroups of patients in comparison with that of tumor-free control group. Additionally, nocturnal melatonin concentrations as well as area under curve were significantly lower in advanced stage of cancer (stages 3 and 4) in comparison with patients with preinvasive cancer (stage 0) at 24:00, 02:00, and 04:00 hours and patients with stage 1 disease at 02:00 and 04:00 hours. The results of the present study indicate that the presence of cervical cancer influences melatonin levels in women. Moreover, stage dependence in reduction of melatonin concentrations has been found.

An assessment of the value of Stereotactic Mammotomy Biopsy (SMB) in the diagnosis of impalpable breast lesions

Summary Background Breast cancer is the most common malignancy for women in Poland and represents 19.7% of all neoplasms diagnosed in this group. It is also the most frequent cause of cancer related deaths among women (14.1% of total). An improvement in these results has been achieved by the popularisation of prophylactic mammography. An increase in awareness among women, of the dangers of breast cancer, and an increase in the availability of mammography testing has resulted in impalpable breast lesions being diagnosed increasingly frequently. These diagnoses require histopathological verification. Aim To demonstrate the usefulness of stereotactic mammotomy biopsy (SMB)in the diagnosis of impalpable breast lesions, and its effects on the processes of diagnosis, classification and treatment of pre-invasive growths within the breast. Materials/Methods Stereotactic mammotomy biopsy is a minimally invasive method for the collection of tissue from impalpable changes in the breast which are visible in mammography images and require histopathological diagnosis. The procedure may be carried out on an ambulant patients, under a local anaesthetic. Between April, 2000, and August, 2003, the First Surgical Department carried out 2000 SMB procedures. Changes suitable for biopsy fall into three groups: clusters and areas of microcalcification – 929 (46.45%), small tumours and soft tissue density – 975 (48.75%), radial structures – 96 (4.80%). Results 365 patients (18.25%)required surgery for the purpose of obtaining a histopathological diagnosis, including 150 (7.50%)with invasive cancer, 120 (6.00%)with preinvasive cancer – DCIS and 95 (4.75%)with atypical ductal hyperplasia – ADH. Among the remaining 1635 patients (81.75%)changes were found to be benign and the patients avoided surgery. Conclusions It is demonstrated that stereotactic mammotomy biopsy is the method of choice for the diagnosis of mammographically detected, inpalpable lesions of the breast, and furthermore, contributes to the process of diagnosis, classification and treatment of pre-invasive growths in the breast.