Journal of clinical pathology 04/2013; · 2.43 Impact Factor
ABSTRACT: Objective: The Ki-67 proliferation index has received an important role in treatment tailoring and molecular classification of estrogen receptor-positive breast carcinomas. The aim was to analyze the reproducibility of assessing proliferation on the basis of Ki-67 immunohistochemistry. Methods: Thirty core biopsy samples of breast cancer patients were analyzed after immunostaining with B56, SP6 and MIB-1 monoclonal Ki-67 antibodies. All samples were evaluated twice and independently by 3 pathologists, with each observer performing his daily routine practice. The ratio of Ki-67-positive cells was estimated with 5% accuracy. Correlation was calculated for the results of each investigator for all pairs of antibodies and for the results of each antibody for all pairs of investigators. Ki-67 scores were divided into categories of either 4 quarters or into 3 groups reflecting the St. Gallen consensus recommendations with 15 and 30% as cutoff values. The reproducibility of classifying the tumors into these categories was assessed with ĸ statistics. Results: Altogether, 540 evaluations were made. Good to excellent correlation (Spearman's and Pearson's coefficient range 0.74-0.92 and 0.73-0.93, respectively) was noted for the pairwise comparison of antibodies by observer and of observers by antibody. The inter- and intraobserver reproducibility of the Ki-67 score classification into equal quarters (1-25, 26-50, 51-75 and 76-100%) or into 3 categories with cutoffs at 15 and 30% was fair to poor in the middle categories, but moderate to substantial in the low and high ranges. Interobserver differences in practice potentially impacted on less consistent classification. Conclusion: Our results indicate that the three different Ki-67 antibodies tested do not substantially influence the reproducibility of the estimated proliferation rates. Although reproducibility is better in the clinically more relevant distinction of high versus low proliferation, without standardization, the current practice of Ki-67 assessment in many laboratories does not allow proper and consistent therapeutic decision-making.
Pathobiology 12/2012; 80(3):111-118. · 1.18 Impact Factor
ABSTRACT: The optimal locoregional treatment of patients diagnosed with sentinel node (SN) micrometastasis is controversial. A previously reported and validated nomogram was used to calculate the risk of non-SN metastasis in patients with SN micrometastasis over a period of 2 years. Patients were given detailed information about the risk, consequences and treatment options of non-SN involvement, the risk and potential complications of unnecessary completion axillary lymph node dissection (ALND), the imperfectness of the nomogram, and other factors that may influence their selection of further treatment. They also received a questionnaire to monitor factors influencing their decisions. Of the 25 patients participating in the study, 10 have opted for ALND. The only factor that seemed to influence their choice was fear from disease recurrence. Giving detailed information to SN micrometastatic patients is a patient-centered alternative to current recommendations on performing ALND in all such patients or omitting ALND in all of them.
Pathology & Oncology Research 10/2012; · 1.37 Impact Factor
ABSTRACT: Chronic granulomatous inflammation may develop after injecting foreign oily substances into the penis. The disorder affects mainly the site of administration, but regional lymphadenopathy or even systemic disease can occur. We present a 39-year-old man with petroleum jelly-induced penile lesion and unilateral inguinal lymphadenitis mimicking incarcerated inguinal hernia. At hernioplasty no hernial sac was found, but enlarged lymph nodes suspicious for malignancy were identified. The histopathologic findings of these nodes were consistent with mineral oil granuloma. Paraffinoma of the male genitalia can cause various clinical features posing a differential diagnostic dilemma. Regional lymphadenitis may be the main clinical characteristic. Patient's history, physical and histopathological examination are required to establish the diagnosis.
Canadian Urological Association journal = Journal de l'Association des urologues du Canada 08/2012; 6(4):E137-9. · 1.24 Impact Factor
ABSTRACT: Although axillary lymph node dissection (ALND) has been the standard intervention in breast cancer patients with sentinel lymph node (SLN) metastasis, only a small proportion of patients benefit from this operation, because most do not harbor additional metastases in the axilla. Several predictive tools have been constructed to identify patients with low risk of non-SLN metastasis who could be candidates for the omission of ALND. In the present work, predictive nomograms were used to predict a high (>50 %) risk of non-SLN metastasis in order to identify patients who would most probably benefit from further axillary treatment. Data of 1000 breast cancer patients with SLN metastasis and completion ALND from 5 institutions were tested in 4 nomograms. A subset of 313 patients with micrometastatic SLNs were also tested in 3 different nomograms devised for the micrometastatic population (the high risk cut-off being 20 %). Patients with a high predicted risk of non-SLN metastasis had higher rates of metastasis in the non-SLNs than patients with low predicted risk. The positive predictive values of the nomograms ranged from 44 % to 64 % with relevant inter-institutional variability. The nomograms for micrometastatic SLNs performed much better in identifying patients with low risk of non-SLN involvement than in high-risk-patients; for the latter, the positive predictive values ranged from 13 % to 20 %. The nomograms show inter-institutional differences in their predictive values and behave differently in different settings. They are worse in identifying high risk patients than low-risk ones, creating a need for new predictive models to identify high-risk patients.
Pathology & Oncology Research 07/2012; · 1.37 Impact Factor
To evaluate the prognostic significance of primary tumor location and to examine whether the effect of adjuvant radiotherapy
on survival varies according to tumor location in women with axillary node-positive (ALN+) breast cancer (BC).
Patients and Methods:
Data were abstracted from the SEER database for 24,410 women aged 25–95 years, diagnosed between 1988–1997 with nonmetastatic
T1–T2, ALN+ BC. Subgroup analyses were performed using interactions within proportional hazards models. Event was defined
as death from any cause. Prognostic variables were selected using Akaike Information Criteria. Joint significances of subgroups
were evaluated with Wald test.
Median follow-up was 10 years. In joint models, statistically significant interactions were found between tumor location,
nodal involvement, type of surgery, and radiotherapy. Factorial presentation of interactions showed consistent 13% proportional
reduction of mortality in all subgroups, except in women with medial tumors with ≥ 4 ALN+ treated with mastectomy. In this
subgroup, use of radiotherapy was associated with a 16% proportional increase in mortality.
Medial tumor location is a significant adverse prognostic factor that should be considered in treatment decision- making for
women with ALN+ BC. Improved survival was observed with radiotherapy use in all subgroups, except in women with medial tumors
with ≥ 4 ALN+ treated with postmastectomy radiotherapy. These findings raise concern that the favorable effect of radiotherapy
may be offset by excess toxicities in the latter subgroup.
Untersuchung der prognostischen Bedeutung der intramammären Tumorlokalisation beim nodal positiven Mammakarzinom und Evaluation
des Einflusses einer adjuvanten Strahlentherapie in Abhängigkeit von der Tumorlokalisation.
Patienten und Methodik:
Die Daten von 24 410 Patientinnen im Alter von 25–95 Jahren mit Erstdiagnose eines Mammakarzinoms T1–T2 N1–3 M0 in den Jahren
1988–1997 wurden der SEER-Datenbank entnommen. Subgruppenanalysen wurden auf der Grundlage von Interaktionstests durchgeführt.
Als Zensurereignisse wurden Todesfälle jeglicher Ursache zugrunde gelegt. Prognostische Kovariaten wurden anhand der Akaike-Kriterien
Die mediane Nachbeobachtungszeit betrug 10 Jahre. In gemeinsamen Rechenmodellen wurden signifikante Interaktionen zwischen
Tumorlokalisation, axillärem Lymphknotenstatus, Operationsart und Strahlentherapie festgestellt. Die faktorielle Verarbeitung
der Interaktionen bestätigte eine konsistente Senkung des Letalitätsrisikos durch eine adjuvante Strahlentherapie um 13% in
allen untersuchten Subgruppen außer bei Patientinnen mit einem medialen Tumorsitz mit mehr als drei Lymphknotenmetastasen
nach Mastektomie. In diesem Patientinnenkollektiv führte die Strahlentherapie zu einer relativen Letalitätserhöhung um 16%.
Medialer Tumorsitz ist ein signifikanter negativer Prognosefaktor bei Patientinnen mit einem nodal positiven Mammakarzinom
und sollte in die Therapieentscheidung dieser Patientinnen mit einbezogen werden. Eine Mortalitätssenkung durch eine adjuvante
Strahlentherapie konnte für alle Patientinnen außer jene mit einem medialen Tumorsitz mit vier und mehr Lymphknotenmetastasen
nach Mastektomie nachgewiesen werden. Diese Ergebnisse geben Anlass zu der Spekulation, dass die therapieassoziierte Morbidität
der Strahlentherapie bei diesen Patientinnen den Therapievorteil der Radiotherapie übersteigen könnte.
Strahlentherapie und Onkologie 04/2012; 185(3):161-168. · 3.56 Impact Factor
ABSTRACT: The optimal technique for sentinel lymph node biopsy (SLNB) is still debated. SLNB with peritumoral injection of Patent blue
dye was performed in 129 clinically T1-T2 and NO breast cancers in 127 patients (group A); it was later replaced by combined
dye and radiocolloid-guided SLNB preceded by lymphoscintigraphy in 72 breast cancer patients (group B). This study compares
these two methods. All patients underwent completion axillary dissection. Means of 1.4 and 1.3 SLNs were identified in groups
A and B, respectively. The mean number of non-SLNs for the whole series was 14.9 (range 5–42). The first 53 cases of lymphatic
mapping (dye only) comprised the institutional learning period during which the identification rate of at least 1 SLN in 30
consecutive attempts reached 90%. The identification rate for the subsequent 76 group A patients was 92%. The accuracy rate
of SLNBs for overall axillary nodal status prediction and the false-negative rate for group A patients (after excluding the
learning-phase cases) were 93% and 10%, respectively. All 72 group B cases had at least one SLN identified, and only one false-negative
case occurred in this group (accuracy and false-negative rates of 99% and 3%, respectively). Both the dye-only and the combined
SLNB methods are suitable for SLN identification, but the latter works better and results in higher accuracy, a higher negative
predictive value, and a lower false-negative rate. It is therefore the method of choice.
La technique optimale pour identifier le ganglion sentinelle (GS) est toujours débattèe. On a injecté en péritumorale, dans
le but d’une biopsie d’un GS, du bleu Patent chez 127 patientes porteuses de 129 tumeurs du sein, classées T1–T2 et NO cliniquement
(Groupe A); cette méthode a été remplacée ultérieurement par l’utilisation de la combinaison de colorant et de biopsie de
GS précédée d’une lymphoscintigraphie chez 72 patientes porteuses de cancer de sein (Groupe B). Cette étude compare les deux
méthodes de biopsie du GS. Toutes les patientes ont eu une lymphadénectomie axillaire. On a identifié 1.4 et 1.3 GS en moyenne,
respectivement, dans les groupes A et B. Le taux moyen pour toute la série a été de 14.9 (extrêmes 5–42). Les 53 premiers
cas de cartographie lymphatique (colorant uniquement) ont été considérés comme la période d’apprentissage initial, pendant
laquelle l’identification d’au moins un GS a atteint 90% parmi les 30 premiers essais consécutifs. Par la suite, le taux d’identification
dans le groupe A a été de 92%. La précision de la biopsie des GS pour la prédiction d’atteinte ganglionnaire globale et le
taux de faux négatifs pour le groupe A (après exclusion des cas de la courbe d’apprentissage) ont été, respectivement, de
93% et de 10%. On a identifié au moins un GS chez toutes les 72 patientes du groupe B, et seulement un faux négatif a été
reconnu dans ce groupe, c’est-à-dire une précision et un taux de faux négatifs de, respectivement, 99% et 3%. L≐utilisation
du colorant seul ou de l’ensemble colorant/lymphoscintigraphie est valable pour l’identification du GS, mais, pour cette dernière,
l’efficacité et la précision sont meilleures, la valeur prédictive négative plus élevée et le taux de faux-négatifs plus bas.
c’est donc la méthode de choix.
Todavía existe controversia sobre cual es la mejor técnica para la realización de la biopsia del ganglio centinela (SLNB).
La SLNB mediante la sola inyección peritumoral del contraste Patent azul se utilizó en 129 cánceres de mama en estadio T1–T2
N0, correspondientes a 127 pacientes (grupo A). Más tarde se sustituyó esta técnica por una SLNB guiada por la utilización
conjunta del colorante vital y de radiocoloides, precedida por una linfoescintigrafía. Este método se empleó en 72 pacientes
con cáncer de mama (grupo B). En todos los pacientes se realizó un vaciamiento completo de axila. Un promedio de 1.4 y 1.3
SLN se identificaron en el grupo A y en el B. Los primeros 53 casos de cartografía linfática (sólo con colorante vital) constituyen
el periodo de aprendizaje durante el cual se identificó al menos 1 SLN en 30 pacientes consecutivos, por lo que el porcentaje
de identificación alcanzó el 90%. El porcentaje de identificación en los 76 pacientes restantes del grupo A fue del 92%. La
precisión de la SLNB para el pronóstico global del estadio ganglionar axilar y el porcentaje de falsos negativos en pacientes
del grupo A (exclusión hecha de los casos utilizados durante el periodo de aprendizaje) fue respectivamente del 93% y 10%.
En los 72 casos del grupo B se identificó, como mínimo, 1 SLN registrándose tan solo 1 falso negativo lo que implica una exactitud
del 99% y un porcentaje de falsos negativos del 3%. Tanto el contraste vital solo como asociado a una escintografía son métodos
apropiados para la SLNB y la identificación del ganglio centinela (SLN) pero la asociación de ambos métodos es mejor, pues
proporciona una gran exactitud, mayores valores predictivos negativos, y menor porcentaje de falsos negativos. Por ello, constituye
el método de elección.
World Journal of Surgery 04/2012; 26(5):592-597. · 2.36 Impact Factor
ABSTRACT: To assess the reliability of nodal staging in colorectal carcinomas (CRCs) when only lymph nodes close to the tumour are recovered and examined histologically.
Lymph nodes from CRC resection specimens were recovered into two fractions: one from around the tumour and the 3 cm sidelong bowel segment associated with it in the proximal and distal directions, and another from the remaining part of the resection specimen.
Of the 762 CRCs (239 right colon, 251 left colon, 257 rectum, 15 unspecified localisation) there were 393 node-negative and 369 node-positive cases. The median number of LNs examined was 18. The assessment of the LNs located in the close fraction (median 13) yielded an adequate qualitative nodal status in 756 patients (99.2%). In four cases (two rectal and two right colic), no LN metastases could be identified in the close-fraction lymph nodes, but nodes from the distant fraction contained metastases. Of the node-positive carcinomas which had at least one positive lymph node in the close fraction, 203 belonged to the pN1 category and 162 to the pN2 category of the Tumour Node Metastasis staging system. Only 14 cases (10 rectal, two right and two left colic tumours) were misclassified as pN1 (on the basis of lymph nodes recovered from the close fraction) although they were of the pN2 category.
In general, nodal status of CRCs may be adequately assessed by examining the lymph nodes from the close fraction around the tumour and the 3 cm sidelong bowel segment in both directions.
Journal of clinical pathology 01/2011; 64(1):13-5. · 2.43 Impact Factor
ABSTRACT: Estrogen receptor (ER) testing has become an important part of breast cancer reporting as the ER status is a predictor of hormonal treatment efficacy. Progesteron receptors (PR) are often tested in parallel, and the best response to hormonal manipulations can be expected in tumors positive for both receptors. The existence of breast cancers with an ER negative and PR positive phenotype is controversial. A series of cases with this phenotype were reevaluated to clarify the existence and the frequency of this entity. A total of 205/6587 (3.1%; range of the rate per department: 0.3-7.1%.) cases reported to have the ER-negative and PR-positive status by immunohistochemistry were collected from 9 Hungarian departments. After careful reevaluation of the tumor slides and control tissues with a 1% cut-off for positivity and restaining of the questionable cases, all but 1 of the reevaluable 182 cases changed their original phenotype. Most cases converted to dual positives (n = 124) or dual negatives (n = 31) or unassessable / questionable. ER-negative and PR-positive breast cancers are very rare if existing. Such a phenotype should prompt reassessment.
Pathology & Oncology Research 01/2011; 17(3):663-8. · 1.37 Impact Factor
ABSTRACT: Isolated tumour cells and micrometastases represent two different staging categories and are often dealt with differently when identified in sentinel lymph nodes of breast cancer patients. The reproducibility of these categories was found to be suboptimal in several studies. The new edition of the TNM (Tumour Node Metastasis) is expected to improve the reproducibility of these categories. Fifty cases of possible low-volume nodal involvement were represented by one to four digital images and were analysed by members of the European Working Group for Breast Screening Pathology (EWGBSP). The kappa value for interobserver agreement of the pN (TNM) staging categories and of the isolated tumour cells category were 0.55 and 0.56 reflecting moderate reproducibility, and the kappa of the micrometastatic category (0.62) reflected substantial reproducibility. This is an improvement over the results gained on the basis of the previous edition of the TNM. Maximal adherence to the category definitions supplemented by explanatory texts in the staging manual should result in more homogeneous nodal staging of breast cancer.
European journal of cancer (Oxford, England: 1990) 12/2010; 47(6):887-94. · 4.12 Impact Factor
ABSTRACT: To assess venous invasion (VI) and its relation to distant metastases in colorectal cancer (CRC).
Primary untreated CRC cases were assessed for VI. All tumour blocks were stained with H&E and orcein. The presence of VI and nodal status were then correlated with the presence of synchronous or metachronous distant metastases.
VI was detected more frequently with the orcein stain (18% versus 71%). Eleven tumours (nine node-positive tumours, all VI positive) were associated with synchronous distant metastasis. During a median follow-up of 17 months nine further cases were diagnosed with distant metastasis (six node-positive tumours, all VI positive). The specificity and sensitivity of the presence of nodal metastasis for predicting distant metastasis were 0.56 and 0.75, respectively. The same values for orcein-detected VI were 0.39 and 1, respectively.
Elastic stains such as the orcein stain enable the detection of clinically relevant VI with greater frequency than conventionally stained histological slides. If nodal involvement is an indication for systemic chemotherapy, the data presented here suggest that VI detected by the orcein stain should also be an indication for systemic chemotherapy.
Journal of clinical pathology 07/2010; 63(7):575-8. · 2.43 Impact Factor
ABSTRACT: The number of positive axillary nodes is a strong prognostic factor in breast cancer, but is affected by variability in nodal staging technique yielding varying numbers of excised nodes. The nodal ratio of positive to excised nodes is an alternative that could address this variability. Our 2006 review found that the nodal ratio consistently outperformed the number of positive nodes, providing strong arguments for the use of nodal ratios in breast cancer staging and management. New evidence has continued to accrue confirming the prognostic significance of nodal ratios in various worldwide population settings. This review provides an updated summary of available data, and discusses the potential application of the nodal ratio to breast cancer staging and prognostication, its role in the context of modern surgical techniques such as sentinel node biopsy, and its potential correlations with new biologic markers such as circulating tumor cells and breast cancer stem cells.
Future Oncology 12/2009; 5(10):1585-603. · 3.16 Impact Factor
ABSTRACT: Small breast cancers often require different treatment than larger ones. The frequency and predictability of further nodal involvement was evaluated in patients with positive sentinel lymph nodes and breast cancers < or =15 mm by means of 8 different predictive tools. Of 506 patients with such small tumors 138 with positive sentinel nodes underwent axillary dissection and 39 of these had non-sentinel node involvement too. The Stanford nomogram and the micrometastatic nomogram were the predictive tools identifying a small group of patients with low probability of further axillary involvement that might not require completion axillary lymph node dissection. Our data also suggest that the Tenon score can separate subsets of patients with a low and a higher risk of non-sentinel node metastasis. Predictive tools based on multivariate models can help in omitting completion axillary dissection in patients with low risk of non-sentinel lymph node metastasis based on their small tumor size.
Orvosi Hetilap 11/2009; 150(48):2182-8.
ABSTRACT: Several models have previously been proposed to predict the probability of non-sentinel lymph node (NSLN) metastases after a positive sentinel lymph node (SLN) biopsy in breast cancer. The aim of this study was to assess the accuracy of two previously published nomograms (MSKCC, Stanford) and to develop an alternative model with the best predictive accuracy in a Czech population. In the basic population of 330 SLN-positive patients from the Czech Republic, the accuracy of the MSKCC and the Stanford nomograms was tested by the area under the receiver operating characteristics curve (AUC). A new model (MOU nomogram) was proposed according to the results of multivariate analysis of relevant clinicopathologic variables. The new model was validated in an independent test population from Hungary (383 patients). In the basic population, six of 27 patients with isolated tumor cells (ITC) in the SLN harbored additional NSLN metastases. The AUCs of the MSKCC and Stanford nomograms were 0.68 and 0.66, respectively; for the MOU nomogram it reached 0.76. In the test population, the AUC of the MOU nomogram was similar to that of the basic population (0.74). The presence of only ITC in SLN does not preclude further nodal involvement. Additional variables are beneficial when considering the probability of NSLN metastases. In the basic population, the previously published nomograms (MSKCC and Stanford) showed only limited accuracy. The developed MOU nomogram proved more suitable for the basic population, such as for another independent population from a mid-European country.
Pathology & Oncology Research 06/2009; 15(4):733-40. · 1.37 Impact Factor
ABSTRACT: To evaluate the prognostic significance of primary tumor location and to examine whether the effect of adjuvant radiotherapy on survival varies according to tumor location in women with axillary node-positive (ALN+) breast cancer (BC).
Data were abstracted from the SEER database for 24,410 women aged 25-95 years, diagnosed between 1988-1997 with nonmetastatic T1-T2, ALN+ BC. Subgroup analyses were performed using interactions within proportional hazards models. Event was defined as death from any cause. Prognostic variables were selected using Akaike Information Criteria. Joint significances of subgroups were evaluated with Wald test.
Median follow-up was 10 years. In joint models, statistically significant interactions were found between tumor location, nodal involvement, type of surgery, and radiotherapy. Factorial presentation of interactions showed consistent 13% proportional reduction of mortality in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with mastectomy. In this subgroup, use of radiotherapy was associated with a 16% proportional increase in mortality.
Medial tumor location is a significant adverse prognostic factor that should be considered in treatment decision- making for women with ALN+ BC. Improved survival was observed with radiotherapy use in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with postmastectomy radiotherapy. These findings raise concern that the favorable effect of radiotherapy may be offset by excess toxicities in the latter subgroup.
Strahlentherapie und Onkologie 04/2009; 185(3):161-8; discussion 169. · 3.56 Impact Factor
ABSTRACT: Colorectal carcinomas (CRCs) infiltrating through the muscularis propria layer without infiltration of adjacent structures, organs or the serosa-i.e. the pT3 tumors, compose the largest subset of large intestinal carcinomas treated by surgical resection. They are heterogeneous in terms of prognosis. CRCs treated by surgery in a period of 69 months were prospectively classified as pT3a tumors (invading to a maximum of 5 mm beyond the muscularis propria) and pT3b tumors (invading deeper). Their nodal status, incidence of vascular invasion and the presence or absence of distant metastases were analyzed in relation to the depth of invasion. Of the 593 CRCs primarily treated by surgery 429 were pT3 tumors. CRCs categorized as pT3a had significantly lower rates of nodal involvement (44% vs 75%), massive nodal involvement (pN2) (9% vs 39%), venous invasion (17% vs 30%) and distant metastasis (11% vs 28%) than pT3b tumors. Significant differences in these prognostic variables in pT3a and pT3b cancers were observed both for carcinomas of the colon and those of the rectum. Such differences were not obvious in further 66 ypT3 cases of rectal carcinoma receiving neoadjuvant treatment before surgery. Tumors in the pT3a category are associated with a better prognostic profile than pT3b tumors. This subdivision might be useful in both prognostication and treatment planning.
Pathology & Oncology Research 02/2009; 15(3):527-32. · 1.37 Impact Factor
ABSTRACT: Granular cell tumor is generally benign, but rare malignant cases have been documented. Features of malignancy include necrosis, cellular spindling, vesicular nuclei with large nucleoli, increased mitotic activity, high nuclear to cytoplasmic ratio, and pleomorphism, but not vascular invasion. Venous invasion was incidentally identified with the orcein elastic stain in an otherwise benign granular cell tumor (propositus case). Four further benign granular cell tumors were also analyzed; venous invasion was discovered in three. It is suggested that vascular invasion is not uncommon in granular cell tumors and should not lead to the classification of the tumor as malignant or atypical. It is likely that in most cases there is only invasion of the vascular wall. It is also suggested that some cases of vascular invasion identified by elastic stains in tumors such as colorectal carcinomas (where these stains are recommended for routine use) may also represent invasion of vascular structures without the propensity of metastasis.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 01/2009; 454(2):211-5. · 2.49 Impact Factor
ABSTRACT: The aim of this work is to report the preliminary results of the Hungarian multicentric randomised DCIS study. Between 2000 and 2007, 278 patients with ductal carcinoma in situ (DCIS) treated by breast-conserving surgery were randomised according to predetermined risk groups. Low/intermediate-risk patients (n=29) were randomised to 50 Gy whole-breast irradiation (WBI) or observation. High-risk cases (n=235) were allocated to receive 50 Gy WBI vs. 50 Gy WBI plus 16 Gy tumour bed boost. Very high-risk patients (patients with involved surgical margins; n=14) were randomised to 50 Gy WBI plus 16 Gy tumour bed boost or reoperation (reexcision plus radiotherapy or mastectomy alone). Immunohistochemistry (IHC) was performed to detect the expression of potential molecular prognostic markers (ER, PR, Her2, p53, Bcl-2 and Ki-67). At a median follow-up of 36 months no recurrence was observed in the low/intermediate- and very high-risk patient groups. In the high-risk group, 4 (1.7%) local recurrences and 1 (0.4%) distant metastasis occurred. No patient died of breast cancer. In the high-risk group of patients, the 3- and 5-year probability of local recurrence was 1.1% and 3.1%, respectively. The positive immunostaining for Her2 (38%), p53 (37%) and Ki-67 (44%) correlated with a high nuclear grade. Significant inverse correlation was found between the expression of ER (77%), PR (67%), Bcl-2 (64%) and grade. Preliminary results suggest that breast-conserving surgery followed by radiotherapy yields an annual local recurrence rate of less than 1% in patients with DCIS. IHC of molecular prognostic markers can assist to gain insight into the biologic heterogeneity of DCIS.
Magyar Onkológia 10/2008; 52(3):269-77.
ABSTRACT: Breast cancers with nodal isolated tumour cells (ITC) and micrometastases are categorised as node-negative and node-positive, respectively, in the tumour node metastasis (TNM) classification. Two recently published interpretations of the TNM definitions were applied to cases of low-volume sentinel lymph node (SLN) involvement and their corresponding non-SLNs for reclassification as micrometastasis or ITC. Of the 517 cases reviewed, 82 had ITC and 435 had micrometastasis on the basis of one classification, and the number of ITC increased to 207 with 310 micrometastases on the basis of the other. Approximately 24% of the cases were discordantly categorised. The rates of non-SLN metastases associated with SLN ITCs were 8.5% and 13.5%, respectively. Although the second interpretation of low-volume nodal stage categories has better reproducibility, it may underestimate the rate of non-SLN involvement. The TNM definitions of low-volume nodal metastases need to be better formulated and supplemented with visual information in the form of multiple sample images.
European journal of cancer (Oxford, England: 1990) 09/2008; 44(15):2185-91. · 4.12 Impact Factor
ABSTRACT: Breast cancer in the young is considered a special clinical presentation of the disease. Sixty-nine breast cancer cases diagnosed at or before the age of 35 were analyzed for common morphological and immunophenotypical features of basal-like carcinomas. Sixteen carcinomas displayed the immunophenotypical characteristics (estrogen receptor and HER2 negativity and positivity for at least one of the following basal markers: cytokeratin 5 or 14, epidermal growth factor receptor, p63) of basal-like carcinomas, and most of them demonstrated characteristic histological features (pushing borders, lymphocytic peritumoral infiltrate, central hypocellular zone or necrosis, high mitotic rate) too. These tumors were more likely to be high-molecular-weight cytokeratin: 34betaE12 and p53 positive by immunohistochemistry. The presence of a basal-like phenotype can be important as concerns systemic treatment issues and could theoretically be associated with a higher rate of BRCA1 mutations in the young, because of the overlap of BRCA1 mutation associated breast carcinomas and the basal-like phenotype.
Pathology & Oncology Research 09/2008; 15(1):41-5. · 1.37 Impact Factor