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1.
Eur J Radiol ; 168: 111119, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37813006

ABSTRACT

PURPOSE: To describe in detail the special features of a previously unappreciated "classic invasive lobular carcinoma" which is confined to the terminal ductal lobular units (TDLUs) and differs considerably from the extensive classic invasive lobular carcinoma, and to suggest specific terminology. METHOD: All invasive breast cancer cases without associated microcalcifications diagnosed in our Institution with the histopathologic diagnosis of classic invasive lobular carcinoma during the years 1996-2019 (n = 560) formed the basis of this study. The cases were prospectively classified according to their imaging biomarkers (mammographic features) and followed up to Dec 31, 2021, to determine long-term patient outcome. An additional 2600 invasive breast cancer cases (diagnosed other than invasive lobular carcinoma) without associated microcalcifications served as a reference group. Detailed histopathologic analysis used large format (10x8 cm) thin section technique and staining methods including hematoxylin-eosin (H&E), E-cadherin, cytokeratin CK 5/6, a transmembrane glycoprotein (CD44) and anti-actin or anti-smooth muscle myosin heavy chain. RESULTS: The imaging biomarkers differentiated two separate disease subgroups, having the same histopathologic diagnosis, classic invasive lobular carcinoma. One of these has the imaging biomarker of extensive architectural distortion with no central tumour mass, occupies the extralobular mesenchyme and has a long-term survival of 56%. The other subgroup forms stellate or circular non-calcified tumour masses usually smaller than 20 mm, which appear to arise in the intralobular mesenchyme, and has a significantly better long-term survival of 84%. CONCLUSIONS: There is a striking difference between the subgross histopathology and the mammographic appearance (imaging biomarkers) of two breast malignancies having the same histopathologic diagnosis, "classic invasive lobular carcinoma". The large difference in the long-term outcome of these two tumour types is even more striking. Using the same specific term, "classic invasive lobular carcinoma", to describe these two separate entities can adversely affect management decisions.


Subject(s)
Breast Neoplasms , Calcinosis , Carcinoma in Situ , Carcinoma, Ductal, Breast , Carcinoma, Lobular , Humans , Female , Carcinoma, Lobular/diagnostic imaging , Carcinoma, Lobular/pathology , Carcinoma in Situ/pathology , Breast Neoplasms/pathology , Mammography , Biomarkers , Carcinoma, Ductal, Breast/pathology
2.
Eur J Radiol ; 166: 111021, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37542814

ABSTRACT

PURPOSE: The development and refinement of breast imaging modalities offer a wealth of diagnostic information such as imaging biomarkers, which are primarily the mammographic appearance of the various breast cancer subtypes. These are readily available preoperatively at the time of diagnosis and can enhance the prognostic value of currently used molecular biomarkers. In this study, we investigated the relative utility of the molecular and imaging biomarkers, both jointly and independently, when predicting long-term patient outcome according to the site of tumour origin. METHODS: We evaluated the association of imaging biomarkers and conventional molecular biomarkers, (ER, PR, HER-2, Ki67), separately and combined, with long-term patient outcome in all breast cancer cases having complete data on both imaging and molecular biomarkers (n = 2236) diagnosed in our Institute during the period 2008-2019. Large format histopathology technique was used to document intra- and intertumoural heterogeneity and select the appropriate foci for evaluating molecular biomarkers. RESULTS: The breast cancer imaging biomarkers were strongly predictive of long-term patient outcome. The molecular biomarkers were predictive of outcome only for unifocal acinar adenocarcinoma of the breast (AAB), but less reliable in the multifocal AAB cases due to variability of molecular biomarkers in the individual tumour foci. In breast cancer of mesenchymal origin (BCMO), conventionally termed classic invasive lobular carcinoma, and in cancers originating from the major lactiferous ducts (ductal adenocarcinoma of the breast, DAB), the molecular biomarkers misleadingly indicated favourable prognosis, whereas the imaging biomarkers in BCMO and DAB reliably indicated the high risk of breast cancer death. Among the 2236 breast cancer cases, BCMO and DAB comprised 21% of the breast cancer cases, but accounted for 45% of the breast cancer deaths. CONCLUSIONS: Integration of imaging biomarkers into the diagnostic workup of breast cancer yields a more precise, comprehensive and prognostically accurate diagnostic report. This is particularly necessary in multifocal AAB cases having intertumoural heterogeneity, in diffuse carcinomas (DAB and BCMO), and in cases with combined DAB and AAB. In such cases, the imaging biomarkers should be prioritised over molecular biomarkers in planning treatment because the latter fail to predict the severity of the disease. In combination with the use of the large section histopathology technique, imaging biomarkers help alleviate some of the current problems in breast cancer management, such as over- and under-assessment of disease extent, which carry the risk of overtreatment and undertreatment.


Subject(s)
Adenocarcinoma , Breast Neoplasms , Carcinoma, Ductal, Breast , Humans , Female , Breast Neoplasms/pathology , Prognosis , Mammography , Biomarkers, Tumor , Carcinoma, Ductal, Breast/pathology
3.
Int J Oncol ; 52(4): 1189-1197, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29436694

ABSTRACT

Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are characterized by genomic rearrangements and point mutations in the proto-oncogene RET. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a suppressor of various receptor tyrosine kinases, including RET. LRIG1 expression levels are associated with patient survival in many cancer types. In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC. LRIG1 was shown to physically interact with both RET2A and RET2B and to restrict their ligand-independent activation. LRIG1 mRNA levels were downregulated in PTC and MTC compared to normal thyroid gland tissue. There was no apparent association between LRIG1 RNA or protein expression levels and patient survival in the studied cohorts. The transgenic RET2B mice developed pre-cancerous medullary thyroid lesions at a high frequency (36%); however, no overt cancers were observed. There was no significant difference in the incidence of pre-cancerous lesions between Lrig1 wild-type and Lrig1-deficient RET2B mice. In conclusion, the findings that LRIG1 is a negative regulator of RET2A and RET2B and is also downregulated in PTC and MTC may suggest that LRIG1 functions as a thyroid tumor suppressor.


Subject(s)
Carcinoma, Neuroendocrine/genetics , Carcinoma, Papillary/genetics , Gene Expression Regulation, Neoplastic/genetics , Membrane Glycoproteins/genetics , Proto-Oncogene Proteins c-ret/genetics , Thyroid Neoplasms/genetics , Animals , Carcinoma, Neuroendocrine/metabolism , Carcinoma, Papillary/metabolism , Down-Regulation , Humans , Membrane Glycoproteins/metabolism , Mice , Mice, Inbred C57BL , Mice, Transgenic , Proto-Oncogene Mas , Proto-Oncogene Proteins c-ret/metabolism , Thyroid Cancer, Papillary , Thyroid Neoplasms/metabolism
4.
Magy Onkol ; 60(1): 72-7, 2016 03 02.
Article in Hungarian | MEDLINE | ID: mdl-26934354

ABSTRACT

We aimed to refine the methodology for discriminating ductal (DAP) and acinar adenocarcinomas (AAP) of the prostate preoperatively with a high degree of accuracy, and confirm that prostate carcinoma of ductal origin is a more aggressive subtype. Moreover, we intended to evaluate the clinical utility of transrectal ultrasound-guided systematic sextant or octant biopsies in prediction of extracapsular extension (ECE) at radical prostatectomy. A blinded retrospective analysis of 3-dimensional histology specimens from 110 consecutive radical prostatectomy (RP) cases operated between 2000 and 2006 was carried out (average follow-up: 5.1 years). The samples were also analyzed for 9 different biomarkers. We performed a retrospective analysis of 84 cases of patients who underwent transrectal ultrasound-guided systematic sextant (in 60 cases) or octant (in 24 cases) biopsy. The presence of ECE was correlated to the number of positive biopsies on each side of the prostate by chi-square analysis. Sensitivity, specificity, positive and negative predictive values were calculated for both positive (two or three positive biopsies per side) and negative (no or only one positive biopsy per side) test results. The number of positive cores was thereafter combined with two other parameters: prostate-specific antigen (PSA) and Gleason score. 3-dimensional and conventional histology classified 97 cases of AAP and 13 cases of DAP. DAP cases had a significantly greater frequency of pT3a and more advanced cancers (p<0.0001), >20 mm tumor focus (p=0.0020), highgrade PIN (p=0.0079), Gleason score ≥7 (p<0.0001), positive surgical margin (p=0.0219), ECE (p<0.0001), vascular invasion (p=0.0033), seminal vesicle infiltration (p=0.0213), biochemical/local recurrence (p=0.0015), regional lymph node metastases and distant metastases (p<0.0001). Three biomarkers in combination (chromogranine A, EGFR, p53) distinguished DAP from AAP with an accuracy of 94% (AUC 0.94; 95% CI: 0.88-0.99). ECE was evidenced at RP in 24% (20/84) of the patients. Chi-square analysis demonstrated a significant correlation between the number of positive biopsies and presence of ECE. Analysis of the 168 prostate sides and dominant sides revealed that systematic needle biopsies had a positive predictive value of 46.7% and 37% and a negative predictive value of 89%, and 94%, respectively. Combination of parameters (biopsy Gleason score ≥7 vs. <7, PSA >10 ng/ml vs. ≤10 ng/ml and more than one positive cores vs. 0 or 1 positives) identified patients at high or low risk of ECE, respectively. On the extremes, with only lowrisk parameters none of the 10 patients, while 77% of those with high-risk group had ECE at RP. Both 3-dimensional histology and the three selected biomarkers can accurately distinguish DAP from AAP. This discriminatory ability offers AAP cases less radical treatment regimens and emphasizes the need to develop more effective treatment regimens for DAP cases. The probability of ECE at radical prostatectomy can be accurately predicted based on the number of positive sextant and octant biopsies, solely or in combination with other parameters.


Subject(s)
Prostatectomy , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/surgery , Humans , Male , Neoplasm Staging , Prognosis , Prostate-Specific Antigen , Retrospective Studies
5.
Breast Cancer (Auckl) ; 8: 15-38, 2014.
Article in English | MEDLINE | ID: mdl-24653647

ABSTRACT

The similarity between the structure and function of the breast and prostate has been known for a long time, but there are serious discrepancies in the terminology describing breast and prostate cancers. The use of the large, thick-section (3D) histology technique for both organs exposes the irrationality of the breast cancer terminology. Pathologists with expertise in diagnosing prostate cancer take the anatomic site of cancer origin into account when using the terms AAP (acinar adenocarcinoma of the prostate) and DAP (ductal adenocarcinoma of the prostate) to distinguish between the prostate cancers originating primarily from the fluid-producing acinar portion of the organ (AAP) and the tumors originating either purely from the larger ducts (DAP) or from both the acini and the main ducts combined (DAP and AAP). Long-term patient outcome is closely correlated with the terminology, because patients with DAP have a significantly poorer prognosis than patients with AAP. The current breast cancer terminology could be improved by modeling it after the method of classifying prostate cancer to reflect the anatomic site of breast cancer origin and the patient outcome. The long-term survival curves of our consecutive breast cancer cases collected since 1977 clearly show that the non-palpable, screen-detected breast cancers originating from the milk-producing acini have excellent prognosis, irrespective of their histologic malignancy grade or biomarkers. Correspondingly, the breast cancer subtypes of truly ductal origin have a significantly poorer outcome, despite recent improvements in diagnosis and therapy. The mammographic appearance of breast cancers reflects the underlying tissue structure. Addition of these "mammographic tumor features" to the currently used histologic phenotypes makes it possible to distinguish the breast cancer cases of ductal origin with a poor outcome, termed DAB (ductal adenocarcinoma of the breast), from the more easily managed breast cancers of acinar origin, termed AAB (acinar adenocarcinoma of the breast), which have a significantly better outcome. This simple and easily communicable terminology could lead to better communication between the diagnostic and therapeutic team members and result in more rational treatment planning for the benefit of their patients.

6.
Cancer ; 120(1): 26-34, 2014 Jan 01.
Article in English | MEDLINE | ID: mdl-24127317

ABSTRACT

BACKGROUND: Multiple synchronous, ipsilateral, invasive foci of breast carcinomas are frequent and are associated with a poorer prognosis. Few studies have investigated the prognostic and therapeutic implications of heterogeneity of such foci. METHODS: The authors reviewed the tumor type, grade, and size of all invasive foci in a series of 110 multifocal breast carcinomas documented on large-format slides. Molecular phenotype was determined by immunohistochemistry in tissue microarray blocks using 3 classification systems. The survival of patients who had tumors with microscopic (tumor type and/or grade) heterogeneity and of those who had tumors with phenotypic heterogeneity was compared with the survival of patients who had multifocal homogeneous tumors using Kaplan-Meier curves. The hazard ratio of dying from breast cancer was also calculated. RESULTS: Intertumoral heterogeneity in tumor type and grade was detected in 16 of 110 tumors (14.6%) and in 6 of 110 tumors (5.5%), respectively. The molecular phenotype of invasive tumor foci within the same breast differed in 10% to 12.7% of patients (11-14 of 110 tumors), depending on the classification system used. Patients who had phenotypically heterogeneous, multifocal cancers had a greater risk of dying from disease (HR=2.879; 95%CI=1.084-7.649; P = .034) and had significantly shorter survival (P = .016). Phenotypic differences were most common in patients who had tumors that were homogeneous in terms of tumor type (11 of 18 tumors) and histology grade (14 of 18 tumors). Phenotyping additional tumor foci had the potential to influence the therapeutic decisions in up to 8 patients. CONCLUSIONS: Phenotyping more than 1 invasive focus of multifocal breast carcinomas only if the individual foci deviate microscopically appears to be insufficient, because phenotypic intertumoral heterogeneity may be observed in microscopically identical foci and has potential prognostic and therapeutic consequences.


Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/therapy , Female , Humans , Middle Aged , Neoplasm Invasiveness , Phenotype , Prognosis , Retrospective Studies , Survival Analysis , Tissue Array Analysis
7.
Cancer ; 119(6): 1132-9, 2013 Mar 15.
Article in English | MEDLINE | ID: mdl-23279980

ABSTRACT

BACKGROUND: The prognostic significance of molecular phenotype in breast cancer is well established in the literature. Recent studies have demonstrated that subgross lesion distribution (unifocal, multifocal, and diffuse) and disease extent also carry prognostic significance in this disease. However, the correlation of molecular phenotypes with subgross parameters has not yet been investigated in detail. METHODS: In total, 444 consecutive invasive breast cancers that were documented in large-format histology slides and worked up with detailed radiologic-pathologic correlation were sampled into tissue microarray blocks and stained immunohistochemically to delineate the molecular subtypes. RESULTS: Diffuse or multifocal distribution of the invasive component of breast carcinomas in this series was associated with a 4.14-fold respectively 2.75-fold risk of cancer-related death compared with unifocal tumors irrespective of molecular phenotype. Patients who had human epidermal growth factor receptor 2 (HER2)-positive cancers; estrogen receptor-negative, progesterone receptor-negative, and HER2-negative (triple-negative) cancers; or basal-like cancers had a 2.18-fold, 2.33-fold, and 4.07-fold risk of dying of disease, respectively, compared with patients who had luminal A carcinomas. Unifocal luminal A, HER2-positive, and basal-like cancers were associated with significantly better long-term survival outcomes than their multifocal or diffuse counterparts; luminal B and triple-negative tumors also had the same tendency. In multivariate analysis, patient age, tumor size category, lymph node status, lesion distribution, and molecular phenotypes remained significant. CONCLUSIONS: Multifocality and diffuse distribution of the invasive component were associated with significantly poorer survival in women with breast carcinomas compared with unifocal disease in patients with luminal A, HER2 type, and basal-like cancers. Molecular classification of breast cancer is a powerful tool but gains in power when combined with conventional and subgross morphologic parameters.


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Female , Follow-Up Studies , Humans , Phenotype , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism
8.
Int J Breast Cancer ; 2012: 436141, 2012.
Article in English | MEDLINE | ID: mdl-23097710

ABSTRACT

To compare the lesion distribution and the extent of the disease in ductal and lobular carcinomas of the breast, we studied 586 ductal and 133 lobular consecutive cancers. All cases were documented on large-format histology slides. The invasive component of ductal carcinomas was unifocal in 63.3% (371/586), multifocal in 35.5% (208/586), and diffuse in 1.2% (7/586) of the cases. The corresponding figures in the lobular group were 27.8% (37/133), 45.9% (61/586), and 26.3% (35/133), respectively. When the distribution of the in situ and invasive component in the same tumors was combined to give an aggregate pattern, the ductal carcinomas were unifocal in 41.6% (244/586), multifocal in 31.6% (185/586), and diffuse in 26.8% (157/586) of the cases. The corresponding figures in the lobular category were 15.0% (20/133), 54.2% (72/133), and 30.8% (41/133), respectively. Ductal cancers were extensive in 45.7% (268/586), lobular in 65.4% (87/133) of the cases. All these differences were statistically highly significant (P < 0.0001). While the histological tumor type itself (ductal versus lobular) did not influence the lymph node status, multifocal and diffuse distribution of the lesions were associated with significantly increased risk of lymph node metastases in both ductal and lobular cancers.

9.
APMIS ; 120(6): 510-8, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22583364

ABSTRACT

Recent studies have shown that patients with prostate carcinomas exhibiting ductal differentiation have an unfavourable prognosis compared with those with purely acinar adenocarcinomas. We studied the expression of nine immunohistochemical markers to evaluate their value in delineating carcinomas with and without ductal differentiation. Thirteen tumours showing cellular characteristics and growth patterns typical of ductal differentiation were identified among 110 analysed prostatectomy specimens. The levels of cytoplasmic expression of chromogranine A (69% vs 19%, p = 0.0003) and nuclear expression of p53 (76% vs 12%, p < 0.0001) as well as nuclear expression of Ki-67 (69% vs 26%, p = 0.0047) in the tumour cells, were found to be statistically significantly different in the two tumour categories. Assessment of chromogranine A, p53 and Ki-67 in prostate carcinoma may serve as useful adjunctive diagnostic tools for delineating more aggressive prostate cancer cases exhibiting ductal differentiation.


Subject(s)
Adenocarcinoma/pathology , Carcinoma, Acinar Cell/pathology , Carcinoma, Ductal/pathology , Cell Differentiation/physiology , Prostatic Neoplasms/pathology , Adenocarcinoma/metabolism , Adenocarcinoma/surgery , Adult , Aged , Biomarkers, Tumor/biosynthesis , Carcinoma, Acinar Cell/metabolism , Carcinoma, Acinar Cell/surgery , Carcinoma, Ductal/metabolism , Carcinoma, Ductal/surgery , Chromogranin A/biosynthesis , Humans , Immunohistochemistry/methods , Ki-67 Antigen/biosynthesis , Male , Middle Aged , Prognosis , Prostatectomy/methods , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/surgery , Tumor Suppressor Protein p53/biosynthesis
10.
Scand J Urol Nephrol ; 46(4): 258-66, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22519924

ABSTRACT

OBJECTIVE: The aim of the study was to refine the methodology for discriminating the ductal (DAP) and acinar adenocarcinomas (AAP) of the prostate and confirm that prostate carcinoma of ductal origin is a more aggressive subtype. MATERIAL AND METHODS: A retrospective analysis of 110 consecutive radical prostatectomy cases operated on between 2000 and 2006 and worked up using large-format "two-dimensional" (2D; 4 µm thick) and "three-dimensional" (3D; 1500 µm thick) histology sections was carried out, with an average follow-up of 5.1 years. The same material was also analysed for selected biomarkers in tissue microarray blocks. The most discriminatory biomarkers were then tested on preoperative core biopsy specimens from 24 of these patients. RESULTS: 3D histology classified 97/110 (88%) cases of AAP and 13/110 (12%) DAP, which was then confirmed in 2D specimens. The DAP cases had a significantly greater frequency of pT3a and more advanced cancers, > 20 mm tumour focus, high-grade prostatic intraepithelial neoplasia, Gleason score ≥ 7, positive margin, extracapsular extension, vascular invasion, seminal vesicle infiltration, biochemical/local recurrence, regional lymph-node metastases and distant metastases. Three biomarkers in combination (chromogranin A, epidermal growth factor receptor and p53] distinguished DAP from AAP with an accuracy of 94% (area under the curve 0.94, 95% confidence interval 0.88-0.99). The same high accuracy was achieved using these three biomarkers on the preoperative specimens. CONCLUSIONS: Both 3D histology and the three selected biomarkers can help in accurately distinguishing DAP from AAP. The clear-cut distinction of two forms of prostate cancers by the approach advocated in this paper would allow AAP patients to undergo less radical treatment and would segregate DAP patients into a subset requiring more effective treatment regimens.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Acinar Cell/pathology , Carcinoma, Ductal/pathology , Prostatic Neoplasms/pathology , Adult , Aged , Biopsy , Carcinoma, Acinar Cell/diagnosis , Carcinoma, Acinar Cell/metabolism , Carcinoma, Ductal/diagnosis , Carcinoma, Ductal/metabolism , Chromogranin A/metabolism , ErbB Receptors/metabolism , Histological Techniques , Humans , Immunohistochemistry , Ki-67 Antigen/metabolism , Lymphatic Metastasis/pathology , Male , Middle Aged , Neoplasm Grading , Prognosis , Prostatectomy , Prostatic Intraepithelial Neoplasia/diagnosis , Prostatic Intraepithelial Neoplasia/pathology , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/metabolism , Retrospective Studies , Tenascin/metabolism , Tissue Array Analysis , Tumor Suppressor Protein p53/metabolism
11.
Anticancer Res ; 32(1): 153-61, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22213301

ABSTRACT

BACKGROUND: Patients with tonsillar and base of tongue cancer, which are human papillomavirus (HPV) positive, have a better clinical outcome than those with HPV-negative tumors. The identification of additional predictive markers for response to therapy could still be of great use. MATERIALS AND METHODS: Tumor markers CD44, p16, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), E-cadherin, cyclooxygenase-2 (COX 2), Ki-67, and p27 were analyzed by immunochemistry, and HPV status was tested by polymerase chain reaction (PCR) in tumors from 73 patients and correlated to survival. RESULTS: High intensity CD44 staining (p=0.006) and high EGFR expression (p=0.026) were indicators of poor prognosis, while high p16 expression (p=0.021) and younger age (p=0.002) were positive prognostic markers for disease-specific survival. Furthermore, staining of CD44 (p=0.026) and age (p=0.002) were shown to be strong prognostic markers in multivariate analysis, which should be evaluated further for possible use in clinical practice.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Hyaluronan Receptors/metabolism , Palatine Tonsil/metabolism , Papillomavirus Infections/metabolism , Tongue Neoplasms/metabolism , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/virology , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Male , Middle Aged , Palatine Tonsil/virology , Papillomaviridae/isolation & purification , Papillomavirus Infections/mortality , Papillomavirus Infections/virology , Prognosis , Survival Rate , Tongue Neoplasms/mortality , Tongue Neoplasms/virology
12.
Hum Pathol ; 42(11): 1761-9, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21663941

ABSTRACT

The prognostic information implied in subgross morphologic parameters such as lesion distribution (unifocal, multifocal, or diffuse) and disease extent in breast cancer has remained largely unexplored in the literature. We aimed to test whether these parameters influence survival in breast carcinoma. The parameters were assessed in a series of 574 cases, all documented in large-format histology sections. We used Cox proportional hazards regression accompanied by Kaplan-Meyer survival curves, with P < .05 regarded as significant. The invasive component was unifocal in 62% (311/499), multifocal in 24% (122/499), and diffuse in 5% (26/499) of the cases. Combining the in situ and invasive tumor components resulted in 48% (274/574) unifocal, 25% (141/574) multifocal, and 20% (117/574) diffuse tumors. Sixty percent (347/574) of the tumors were categorized as having limited extent (occupying an area <40 mm in largest dimension) and 29% (164/574) as extensive. Highly significant (P < .0001) differences were observed in 10-year disease-specific cumulative survival among the cases with unifocal, multifocal, and diffuse invasive (89.6%, 76.0%, and 63.6%, respectively) and combined (92.3%, 82.3%, and 75.7%, respectively) lesion distribution. Patients with extensive tumors exhibited a significantly lower cumulative survival (P < .0001) compared with those with limited extent (91.6% and 75.5%) and a statistically significantly 1.89-fold (95% confidence interval, 1.07-3.37; P = .03) risk for breast cancer death after controlling for tumor attributes, type of surgery, and adjuvant therapy. The hazard ratio for breast cancer death for mutifocal and/or diffuse tumors versus unifocal ones was 1.96 (95%; 1.11-3.48; P = .02) after controlling for the same factors. Lesion distribution and disease extent represent important independent survival-related prognostic parameters in breast carcinoma.


Subject(s)
Breast Neoplasms/pathology , Adult , Aged , Breast Neoplasms/mortality , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Invasiveness , Prognosis
13.
Patholog Res Int ; 2011: 480960, 2010 Nov 03.
Article in English | MEDLINE | ID: mdl-21151538

ABSTRACT

We analyzed the subgross distribution of the invasive component in 875 consecutive cases of breast carcinomas using large-format histology sections and compared the immunophenotype (estrogen and progesterone receptor expression, HER2 overexpression and expression of basal-like markers, CK5/6, CK14, and epidermal growth factor receptor) in unifocal, multifocal, and diffuse tumors. Histology grade and lymph node status were also analyzed. Unifocal invasive carcinomas comprised 58.6% (513/875), multifocal invasive carcinomas 36.5% (319/875), and diffuse invasive carcinomas 4.9% (43/875) of the cases. The proportion of lymph node-positive cases was significantly higher in multifocal and diffuse carcinomas compared to unifocal cancers, but no other statistically significant differences could be verified between these tumor categories. Histological multifocality and diffuse distribution of the invasive tumor component seem to be negative morphologic prognostic parameters in breast carcinomas, independent of the molecular phenotype.

14.
Virchows Arch ; 455(2): 109-15, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19621241

ABSTRACT

We analyzed 301 consecutive cases of 1-14-mm invasive breast carcinomas documented in large-format histological sections to determine the distribution of invasive and in situ foci. We also aimed to determine whether this distribution was related to the frequency of demonstrable vascular invasion and lymph node metastases. One third of the carcinomas (31.9%, 96 cases) had a multifocal invasive component and a more than doubled relative risk of vascular invasion (RR = 2.3642, 95% confidence interval (CI) = 1.5077-3.7073) and lymph node metastasis (RR = 2.7760, 95% CI = 1.6337-4.7171) compared to unifocal invasive carcinomas. Invasive carcinomas with diffuse in situ component had an elevated relative risk for vascular invasion (RR = 2.2201, 95% CI = 1.4049-3.5083) and lymph node metastasis (RR = 1.9201, 95% CI = 1.1278-3.2691) compared to those with unifocal or multifocal in situ lesions. However, multifocality of the invasive component was associated with a substantially elevated risk of vascular invasion and lymph node metastasis, even in cases with diffuse in situ component. Similar observations were made in the 1-9- and 10-14-mm invasive carcinoma subgroups. These findings indicate that lesion distribution has prognostic relevance for 1-14-mm invasive breast carcinomas and underline the importance of using special techniques in breast pathology for proper assessment of this parameter.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Neoplasm Metastasis/pathology , Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Female , Humans , Lymphatic Metastasis/diagnosis , Lymphatic Metastasis/pathology , Neoplasm Invasiveness/diagnosis , Neoplasm Invasiveness/pathology , Neoplasm Metastasis/diagnosis , Neovascularization, Pathologic/diagnosis , Neovascularization, Pathologic/pathology , Prognosis , Retrospective Studies
15.
Orv Hetil ; 149(24): 1125-35, 2008 Jun 15.
Article in Hungarian | MEDLINE | ID: mdl-18539579

ABSTRACT

The authors followed the procedure of comparison of clinical and pathological diagnoses. Based on their own data and those from the literature, they examined the diagnostic difficulties of the underlying cause of death, the disturbing factors in the comparison of clinical and pathological diagnoses, and the possibility of resolving them. They suggest to choose a method of comparison which can offer the possibility of analyzing both the nature and causes of discrepancies. This comparison can be realistic only if these issues are studied with the same and uniform method, and the results must be interpreted cautiously.


Subject(s)
Cause of Death , Diagnostic Errors , Pathology, Clinical/methods , Autopsy , Death Certificates , Humans , Pathology, Clinical/standards
16.
Jpn J Clin Oncol ; 34(9): 519-24, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15466825

ABSTRACT

BACKGROUND: After completion of axillary dissection, many breast cancer patients with axillary sentinel nodal involvement are found to have regional disease limited to the sentinel nodes. These patients are exposed to the morbidity of axillary clearance without any expected therapeutic benefit. METHODS: Sentinel node biopsy was performed either with Patent blue dye or with a combined dye, radiocolloid and gamma-probe-guided method involving peritumoral tracer administration. For a series of 150 consecutive patients with involved axillary sentinel nodes and axillary dissection, factors associated with non-sentinel nodal involvement were analysed in a multivariate analysis based on logistic regression with the use of fractional polynomials. RESULTS: The following variables were found to be potentially associated with non-sentinel node metastases: tumour size, sentinel node metastasis size, number of examined sentinel nodes, percentage of involved sentinel nodes (the latter two were found to be significant only when in combination), and extracapsular perinodal spread. CONCLUSIONS: Isolated tumour cells and micrometastases in axillary sentinel nodes carry a low risk of non-sentinel node metastasis. The risk of metastasis to further echelon nodes is higher with macrometastases, especially if there is extracapsular growth and the proportion of involved sentinel nodes is high.


Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/surgery , Lymph Node Excision , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy , Axilla , Female , Humans , Lymphatic Metastasis , Multivariate Analysis , Neoplasm Staging
17.
Pathol Oncol Res ; 8(2): 142-4, 2002.
Article in English | MEDLINE | ID: mdl-12172580

ABSTRACT

Both chromophobe carcinoma and sarcomatoid carcinoma of the kidney are rare. The former is characterized by a relatively good prognosis, while the latter is a highly aggressive tumor. Coexistence of the two components in one renal tumor, which has been reported only rarely, is therefore paradoxical. Both sarcomatoid and chromophobe renal carcinoma were diagnosed in a 52-year-old woman following nephrectomy and resection of metastases in the right lobe of the liver. She died of the disease two months after the first operation; only the sarcomatoid component of her tumor was seen in the liver metastasis and the recurrent carcinoma. Differences in phenotype, immunophenotype and DNA-ploidy patterns of the two components are reported. The intensive p53 staining observed only in the sarcomatoid area supports the role of the TP53 gene in the transformation of chromophobe renal carcinoma to sarcomatoid carcinoma.


Subject(s)
Adenoma, Chromophobe/pathology , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Sarcoma/pathology , Adenoma, Chromophobe/metabolism , Adenoma, Chromophobe/surgery , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/surgery , Fatal Outcome , Female , Humans , Immunophenotyping , Kidney Neoplasms/metabolism , Kidney Neoplasms/surgery , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Middle Aged , Nephrectomy , Ploidies , Sarcoma/metabolism , Sarcoma/surgery , Tumor Suppressor Protein p53/metabolism
18.
Magy Seb ; 55(6): 375-7, 2002 Dec.
Article in Hungarian | MEDLINE | ID: mdl-12616823

ABSTRACT

UNLABELLED: Sentinel lymph node mapping has already been accepted as part of the treatment for malignant melanomas of the skin and in breast carcinomas. The status of lymph nodes is an important prognostic marker in colorectal carcinoma as well. The authors tried the feasibility of this technique in colorectal carcinomas. The technique is analogous to the one used in breast cancer and melanoma: 2 ml of 2.5% Patentblau dye was given subserosally around the tumor. After resection the specimen was immediately sent to pathology where the lymph nodes were removed. This technique has been tried on 31 patients, 22 with colonic and 9 with rectal tumors. Of these patients, 15 were Dukes stage C, 14 were Dukes stage B and 2 were Dukes stage A. An average 4.3 blue lymph nodes were found in colon tumors and 5.4 in rectal tumors and an average 14 unstained lymph nodes were found in colon tumors, and 7 in rectal tumors. The blue nodes were predictive of the nodal status in 9 of the 15 Dukes stage C patients. In these cases the blue lymph nodes contained metastases and there were 2 cases where metastases were limited to the blue lymph nodes. SUMMARY: The authors found a high false negative rate for lymphatic mapping with the vital dye technique, therefore they try to change the method according to that used by Saha et al. The aim of sentinel node identification in colorectal carcinomas would be improved staging rather than reducing of the extent of lymphadenectomy. The role of lymphatic mapping in large bowel cancers needs further investigations. Until the results are reliable, as many lymph nodes as possible have to be excited and sent for histology.


Subject(s)
Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Sentinel Lymph Node Biopsy , Aged , Coloring Agents , False Negative Reactions , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Neoplasm Staging , Rosaniline Dyes
19.
Magy Onkol ; 46(4): 315-21, 2002.
Article in Hungarian | MEDLINE | ID: mdl-12563353

ABSTRACT

This review deals with results attained by Hungarian authors in the field of sentinel nodes and presents the current status of sentinel lymphadenectomy in Hungary. After a short historical overview, results with melanoma and breast cancer are summarized, and feasibility studies on other possible sites (gastrointestinal tract, thyroid gland) are also mentioned. Pathological aspects are also dealt with in a separate section. The summary of these results suggests that Hungarian authors have investigated several facets of sentinel node biopsy, their results are in keeping with international results. Despite the favourable results, the method still needs time to be more widely accepted and reflected in the literature.


Subject(s)
Lymph Nodes/surgery , Neoplasms/pathology , Neoplasms/surgery , Sentinel Lymph Node Biopsy , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Female , Humans , Hungary , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis/diagnosis , Melanoma/pathology , Melanoma/surgery , Skin Neoplasms/pathology , Skin Neoplasms/surgery
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