Sabato 27 ottobre 2012 - Pacini Editore

PoStER
Epidemiological and biomolecular characteristics
of subcentimetric invasive breast carcinoma:
a comparison between two different cohorts
in southern Italy
A. Ieni1 , G. Giuffrè1 , A. Cascone2 , P. Zeppa2 , G. Branca1 , G. Tuccari1,3
1Dipartimento di Patologia Umana, Università di Messina, A.O.U. “Policlinico
G. Martino”, Messina; 2 Dipartimento di Medicina e Chirurgia, Azienda
Ospedaliera Universitaria “San Giovanni di Dio e Ruggi d’Aragona”
Università di Salerno; 3 Programma Interdipartimentale di Citodiagnostica
e Patologia Molecolare, A.O.U. “Policlinico G. Martino”, Messina
Background. Data concerning human epidermal growth factor
receptor 2 gene (HER-2) in pT1a,bN0M0 breast cancer are
conflicting and heterogeneous. In subcentimetric invasive breast
carcinoma (SIBC), high tumor grade is the most significant factor
associated with poor prognosis together with younger age, estrogen/progesterone
receptor–negative status and high Ki-67 index.
However, in the same group, cases HER-2-positive seem to have
an higher risk of relapse and related death, although the usage of
trastuzumab in SIBC is still debatable. In the present study, we
compared HER-2 status, hormone receptor status and Ki67 index
in two cohorts of SIBC from two Institutions in Southern Italy
(Salerno and Messina).
Methods. Sixty-three cases and thirty-five cases of SIBC were
collected from the Universities of Messina and Salerno, respectively.
From formalin-fixed paraffin-embedded tissue blocks
of SIBC 4 µm thick parallel sections were cut, mounted on
silane-coated glasses and, after routine retrieval procedure, immunostained
for ER (ID5, DBA, 1:10), PR (PgR-ICA, Abbott,
1:10), Ki-67 antigen (MIB-1, DAKO Cytomation, 1:200) and
HER-2 (HercepTest AO485 DAKO). HER-2 status was scored
according to manufacturer’s recommendations; equivocal cases
(2+) were further assessed by FISH test (pharmDx DAKO).
Statistical analysis was performed to assess the reproducibility
of data evaluation in the two institutions and then any significant
differences between the two groups for the considered parameters
using the Chi-square test.
Results. SIBC, pT1a cases were 17 (26.98%) in Messina
and 10 (28.5%) in Salerno series, whereas pT1b cases were
46 (73.02%) and 35 (71.5%) respectively. High Ki-67 index
(> 12%) was found in 60% of Messina SIBC cases and 55%
of Salerno ones. As for the hormonal receptors status, ER immunoreactivity
was 85% and 83% and PR 74.9 and 77.1 in two
groups respectively. Finally, considering HER2 status, 15.5%
of cases were amplified in the Messina cohort and 17.2% in the
Salerno one. Chi-square test did not show statistical significant
differences between the two different cohorts for all examined
parameters.
Conclusions. HER-2 status, ER/PR status and Ki67 index in
SIBC are comparable and reproducible in the two institutions
representing two different geographic areas. The merged cohorts
are suitable for further investigations and for the evaluation of the
current guidelines of Trastuzumab treatment in SIBC.
Triple negative breast ductal invasive carcinomas:
further immunohistochemical investigations
A. Ieni1 , V. Barresi1 , R. Cardia1 , C. Crisafulli1 , G. Giuffrè1 ,
G. Ricciardi2 , V. Adamo2 , G. Tuccari1,3 1 Dipartimento di Patologia Umana, Sezione di Anatomia Patologica;
2 3 Dipartimento di Patologia Umana, Sezione di Oncologia Medica; Programma
Interdipartimentale di Citodiagnostica e Patologia Molecolare,
A.O.U. “Policlinico G.Martino”, Università di Messina
Background. Triple-negative breast cancers (TNBC) represents
a subtype of invasive carcinomas, immunoistochemically charac-
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terized by a lock of expression of both oestrogen and progesteron
receptors as well as HER2. This subtype accounts for about
10-17% of all breast cancer and is more commonly seen women
younger than 50 years with elevated frequency of distant metastases
and short oncologic outcome. Morphologic features of TNBC
are considered greater neoplastic size, solid growth pattern, high
proliferative fraction, necrosis, increased apoptotic cells and
generally an infiltrating ductal histotype. To date, chemiotherapy
remains the only possible therapeutic option in the adjuvant or
metastatic setting in the TNBC. In the present study, we have
analyzed the immunohistochemical distribution pattern of some
biomolecular tissue markers, such as DNA topoisomerasi II α
(DT-II α), caveolin-1 (Cav-1), androgenic receptors, e-cadherin
in a cohort of invasive ductal TNBC in order to identify possible
relationship among them and clinico-pathological characteristics
as well as survival.
Methods. From files of the Department of Human Pathology,
seventy-two formalin-fixed paraffin-embedded tissue blocks of
TNBC were obtained from an equal number of female patients
(age range 32-92 yrs, mean 62.1). From each tissue block, 4
µm thick parallel sections were cut, mounted on silane-coated
glasses and subjected to immunohistochemical procedures with
the following antisera: KI-67 (Clone MIB-1; DAKO Corporation,
Glostrup, Denmark; w.d.1:150); DNA Topoisomerasi II
α (clone KI-s1; DAKO; w.d.1:150); E-cadherin (clone NCH
38, DAKO; w.d.1:200); androgenic receptor (clone AR 441,
DAKO; w.d.1:100); Caveolin-1 (Santa Cruz Biotecnology Inc.,
Santa Cruz, California, USA; w.d. 1:500). 3-3’ diaminobenzidine
tetrahydrochloride was utilized as chromogen and a slight
nuclear counterstain was performed by Mayer’s haematoxylin.
Scoring of each immunostaining was done as elsewhere previously
reported. The specificity of the binding was assessed by
omitting the primary antiserum or replacing it with normal rabbit
serum or phosphate buffered saline solution (PBS, pH 7.4).
The Chi-square test was used to evaluate the correlations between
the clinico-pathological variables and all the considered
immunostainings.
Results. pTNM showed that, among ductal invasive TNBC,
16/72 were stage I, 30/72 stage II, 18/72 stage III and only 8/72
stage IV. 36/72 showed metastases regarding the node status.
Although before the study started, the observational period of
patients ranged from 5-152 months, a mean follow-up of 67.7
months was available only for 31 TNBC cases. An increased
growth fraction ((> 10% Ki67 LI) was found in 42/72 patients
(58.3%), while DT-II α (> 13%) was elevated in 40/72 (55.5%).
Androgen receptors were revealed in 19/72 (26.4 %), whereas
a high ID score (4-9) for Cav-1 was calculated in 45/72 cases
(72.5%). Finally, E-cadherin was negative or focally and slightly
present in neoplastic elements of 43/72 patients (59.7%). Statistical
analysis documented a positive correlation between Ki-67 LI
and grade or DNA Topoisomerase II α expression with significant
p values, (p = 0.02) and (p < 0.001), respectively. Moreover,
a significant relationship has been found between Cav-1 and
grade (p = 0.032), Ki-67 LI (p = 0.019) and overall survival and
progression free survival concerning cases in which the followup
was available (p = 0.036). The mean overall survival was 47
months and the mean progression free survival was 27 months.
Finally, parameters significantly related to overall survival were
represented by neoplastic stage (p = 0.011) and Cav-1 immunoreactivity
(p = 0.036).
Conclusions. Among the analyzed immunohistochemical parameters,
Cav-1 appears the most useful approach in ductal invasive
TNBC; moreover, taking into consideration the relationships
exhisting between antracyclines and DT-II α as well as between
taxanes and Cav-1, further insights in targeted oncologic therapy
should be verified in TNBC.