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Imprint cytology in conservative surgical management of breast cancer — A way out of the woods?
164
The Breast
After 5.8 years median follow-up, survival was not impaired74 amongst those who delayed at least six months (53% v 56% 5-year). With i8 months or moreYdelay, a clear survival disadvantage was seen amongst those with stage l-l 1 disease (40% v 69% 5-year, P < 0.001, log rank test). In contrast, when survival was recalculated from date of first symptom, those who delayed 6 months or more apparently lived longer (68% v 54%, P=O.O14). This study shows significant associations between delay in presentation, advanced stage and reduced survival from date of diagnosis. However, if account is taken of the delay before diagnosis, there appears to be a subgroup of patients who delay presentation, who have a high incidence of locally advanced disease and survive at least as long as those who were managed promptly.
72 IMPRINT CYTOLOGY IN CONSERVATIVE SURGICAL MANAGEMENT OF BREAST CANCER - A WAY OUT OF THE WOODS? Desai AJ, Walsh GA, Trott PA, McLennan JA Breast Unit, Royal Marsden Hospital, UK
K, McKinna
Conservative surgery in breast cancer carries with it the risk of inadequate tumour clearance. Confirmation by histopathological examination takes a few days and may be unreliable. In a pilot study in 1991 imprint cytology of the margins appeared to correlate well with histology. The method has now been applied to 133 consecutive biopsies and the results are summarised as follows: There were 30 exclusions because of benign histology or prior combined therapy. 79 were deemed to have clear histological margins. Cytology was negative in 66 of the remaining 13. 3 yielded malignant cells and 10 suspicious cells. 24 excisions were reported histologically as being involved by tumour at the margins. Imprint cytology confirmed this in 13 samples (9 C5,4 C4, 3 C3 and 8 C2). Re-excision confirmed concurrence in 13 (C4 & C5). Of the 8 with C2 cytology at the margins 5 re-excisions yielded no residual tumour (1 patient refused surgery, in 2 the deep margin was involved which was the pectoral fascia). Negative cytology correlates well with negative histology. Positive or suspicious imprint cytology of the margins may be used intraoperatively to ensure adequate tumour clearance. A study is underway at Charing Cross Hospital to determine the value of this form of reporting.
73 ASSESSMENT OF eerbB-2 AMPLIFICATION IN BREAST CANCER BY THE DIFFERENTIAL PCR METHOD Hubbard A L and Anderson T J Department of Pathology, University School, UK
of Edinburgh
Medical
The proto oncogene c-erbB-2 has been associated with aspects of breast cancer, where overexpression of the gene correlated with poor prognosis. However the exact role of the gene in cancer progression is not known. Previously, overexpression and gene amplification have been investigated by immunohistochemistry (IHC) and DNA blotting, but these methods may be either insensitive for low copy number or require large amounts of tumour tissue respectively. Small lesions such as those screen detected or occult have frequently been excluded from these investigations. Differential PCR, which detects c-erbB-2 gene numbers with high sensitivity has been applied to cancers from screened and symptomatic cases of comparable age. The results in 190 cases showed that PCR detected increased cerbB-2 gene copy number in 46%. a considerably higher proportion than that detected by IHC. Frequency of gene amplification was equivalent in node positive and node negative cases, and gene amplification was found in tubular and lobular invasive cancers. These findings in the special types of invasive cancer indicate that the technique offers potential to investigate the varied disregulation of gene function in the progression of breast cancer.
DUCTAL
CARCINOMA
IN-SITU
OF
THE
BREAST: A NEW SIMPLIFIED HISTOLOGICAL CLASSIFICATION. ASSOCIATION BETWEEN CELLULAR PROLIFERATION AND c-erbB-2 PROTEIN EXPRESSION David N. Poller, Marcus H. Galea, Adrian P. Locker, Christopher W. El&on, Roger W. Blarney, Ian 0. Ellis Nottingham City Hospital, UK The diagnosis of Ductal Carcinoma In-Situ Of The Breast (DCIS) has become increasingly common with the advent of breast screening. Classical comedo-type DCIS shows a higher proliferative fraction than cribriform DCIS, with a greater tendency to local recurrence after breast conservation treatment, and a higher frequency of c-erbB-2 protein overexpression than cribrifotm DCIS. The cellular architecture of DCIS. combined with the presence or absence of significant intraductal tumour cell necrosis, c-erbB-2 protein status, and proliferative fraction has been utilised to establish a novel simplified working classification of DCIS with potential biological significance. Proliferation indices (S-phase fraction) were studied in 76 cases of pure DCIS. Tumours were classified according to conventional criteria and also according to a novel simplified classification based on cellular necrosis and morphology. This new classification defines three distinct tumour groups; pure comedo in 19 (25.0%) of cases. DCIS with necrosis (non-pure comedo) in 21 (27.6%) of patients and DCIS without necrosis 36 (47.4%) of cases, the latter group comprising largely classical cribriform or micropapillary architectural subtypes. Flow cytometric DNA analysis showed a significantly higher S-phase fraction in comedo DCIS than in the subgroup of DCIS tumors without necrosis (p < 0.01 (anova]) and a higher S-phase fraction in DCIS with necrosis (non-pure comedo) as compared to DCIS without necrosis (p=O.O17 (annoval). The difference in S-phase fraction between comedo DCIS and the group comprising DCIS with necrosis (non-comedo) did not achieve statistical significance (p=O.O80 (anova)) although the number of tumours in the latter group was small (21 cases). Necrosis in DCIS in the absence of pure classical comedo morphology is a feature of in-situ breast cancer with an intermediate proliferative fraction as compared to the high proliferative fraction of pure comedo DCIS and the low proliferative fraction of DCIS without necrosis. There was no significant difference in DNA ploidy (diploid or aneuploid) between the subgroups as assessed by chi-squared analysis. DCIS with necrosis (non-pure comedo) should be adopted as a distinct histological subgroup of DCIS in future clinical studies of in-situ mammary carcinoma.
75 NON-OPERATIVE MANAGEMENT OF DISCRETE PALPABLE BREAST LUMPS IN WOMEN OVER 35 YEARS OF AGE MH Galea, AR Dixon, G Pye, ID Ellis, CW Elston, EJ Roebuck, AR Wilson, RW Blarney City Hospital, Nottingham, UK Traditional surgical management of discrete palpable breast lumps is excision for accurate histology. However, this is unnecessary as many prove to be benign lesions. 288 symptomatic women over 35 with a discrete palpable breast lump were assessed in a dedicated multidisciplinary clinic, Aug 1989Apr 1991. For a lump to be left in situ the following criteria had to be fulfilled: 1. Clinically lump feels entirely benign 2. Mammography and/or ultrasound benign 3. 2 fine needle aspirations (FNA) showing benign cytology 4. If 1-3 fulfilled, but lump >3cm excision advised 146 lumps were simple cysts; these resolved completely on aspiration. 142 were solid 105 women fulfilled the above criteria: 16 chose operation (histology, benign). 37 women failed the criteria and proceeded to excision biopsy.
The Breast
After 5.8 years median follow-up, survival was not impaired74 amongst those who delayed at least six months (53% v 56% 5-year). With i8 months or moreYdelay, a clear survival disadvantage was seen amongst those with stage l-l 1 disease (40% v 69% 5-year, P < 0.001, log rank test). In contrast, when survival was recalculated from date of first symptom, those who delayed 6 months or more apparently lived longer (68% v 54%, P=O.O14). This study shows significant associations between delay in presentation, advanced stage and reduced survival from date of diagnosis. However, if account is taken of the delay before diagnosis, there appears to be a subgroup of patients who delay presentation, who have a high incidence of locally advanced disease and survive at least as long as those who were managed promptly.
72 IMPRINT CYTOLOGY IN CONSERVATIVE SURGICAL MANAGEMENT OF BREAST CANCER - A WAY OUT OF THE WOODS? Desai AJ, Walsh GA, Trott PA, McLennan JA Breast Unit, Royal Marsden Hospital, UK
K, McKinna
Conservative surgery in breast cancer carries with it the risk of inadequate tumour clearance. Confirmation by histopathological examination takes a few days and may be unreliable. In a pilot study in 1991 imprint cytology of the margins appeared to correlate well with histology. The method has now been applied to 133 consecutive biopsies and the results are summarised as follows: There were 30 exclusions because of benign histology or prior combined therapy. 79 were deemed to have clear histological margins. Cytology was negative in 66 of the remaining 13. 3 yielded malignant cells and 10 suspicious cells. 24 excisions were reported histologically as being involved by tumour at the margins. Imprint cytology confirmed this in 13 samples (9 C5,4 C4, 3 C3 and 8 C2). Re-excision confirmed concurrence in 13 (C4 & C5). Of the 8 with C2 cytology at the margins 5 re-excisions yielded no residual tumour (1 patient refused surgery, in 2 the deep margin was involved which was the pectoral fascia). Negative cytology correlates well with negative histology. Positive or suspicious imprint cytology of the margins may be used intraoperatively to ensure adequate tumour clearance. A study is underway at Charing Cross Hospital to determine the value of this form of reporting.
73 ASSESSMENT OF eerbB-2 AMPLIFICATION IN BREAST CANCER BY THE DIFFERENTIAL PCR METHOD Hubbard A L and Anderson T J Department of Pathology, University School, UK
of Edinburgh
Medical
The proto oncogene c-erbB-2 has been associated with aspects of breast cancer, where overexpression of the gene correlated with poor prognosis. However the exact role of the gene in cancer progression is not known. Previously, overexpression and gene amplification have been investigated by immunohistochemistry (IHC) and DNA blotting, but these methods may be either insensitive for low copy number or require large amounts of tumour tissue respectively. Small lesions such as those screen detected or occult have frequently been excluded from these investigations. Differential PCR, which detects c-erbB-2 gene numbers with high sensitivity has been applied to cancers from screened and symptomatic cases of comparable age. The results in 190 cases showed that PCR detected increased cerbB-2 gene copy number in 46%. a considerably higher proportion than that detected by IHC. Frequency of gene amplification was equivalent in node positive and node negative cases, and gene amplification was found in tubular and lobular invasive cancers. These findings in the special types of invasive cancer indicate that the technique offers potential to investigate the varied disregulation of gene function in the progression of breast cancer.
DUCTAL
CARCINOMA
IN-SITU
OF
THE
BREAST: A NEW SIMPLIFIED HISTOLOGICAL CLASSIFICATION. ASSOCIATION BETWEEN CELLULAR PROLIFERATION AND c-erbB-2 PROTEIN EXPRESSION David N. Poller, Marcus H. Galea, Adrian P. Locker, Christopher W. El&on, Roger W. Blarney, Ian 0. Ellis Nottingham City Hospital, UK The diagnosis of Ductal Carcinoma In-Situ Of The Breast (DCIS) has become increasingly common with the advent of breast screening. Classical comedo-type DCIS shows a higher proliferative fraction than cribriform DCIS, with a greater tendency to local recurrence after breast conservation treatment, and a higher frequency of c-erbB-2 protein overexpression than cribrifotm DCIS. The cellular architecture of DCIS. combined with the presence or absence of significant intraductal tumour cell necrosis, c-erbB-2 protein status, and proliferative fraction has been utilised to establish a novel simplified working classification of DCIS with potential biological significance. Proliferation indices (S-phase fraction) were studied in 76 cases of pure DCIS. Tumours were classified according to conventional criteria and also according to a novel simplified classification based on cellular necrosis and morphology. This new classification defines three distinct tumour groups; pure comedo in 19 (25.0%) of cases. DCIS with necrosis (non-pure comedo) in 21 (27.6%) of patients and DCIS without necrosis 36 (47.4%) of cases, the latter group comprising largely classical cribriform or micropapillary architectural subtypes. Flow cytometric DNA analysis showed a significantly higher S-phase fraction in comedo DCIS than in the subgroup of DCIS tumors without necrosis (p < 0.01 (anova]) and a higher S-phase fraction in DCIS with necrosis (non-pure comedo) as compared to DCIS without necrosis (p=O.O17 (annoval). The difference in S-phase fraction between comedo DCIS and the group comprising DCIS with necrosis (non-comedo) did not achieve statistical significance (p=O.O80 (anova)) although the number of tumours in the latter group was small (21 cases). Necrosis in DCIS in the absence of pure classical comedo morphology is a feature of in-situ breast cancer with an intermediate proliferative fraction as compared to the high proliferative fraction of pure comedo DCIS and the low proliferative fraction of DCIS without necrosis. There was no significant difference in DNA ploidy (diploid or aneuploid) between the subgroups as assessed by chi-squared analysis. DCIS with necrosis (non-pure comedo) should be adopted as a distinct histological subgroup of DCIS in future clinical studies of in-situ mammary carcinoma.
75 NON-OPERATIVE MANAGEMENT OF DISCRETE PALPABLE BREAST LUMPS IN WOMEN OVER 35 YEARS OF AGE MH Galea, AR Dixon, G Pye, ID Ellis, CW Elston, EJ Roebuck, AR Wilson, RW Blarney City Hospital, Nottingham, UK Traditional surgical management of discrete palpable breast lumps is excision for accurate histology. However, this is unnecessary as many prove to be benign lesions. 288 symptomatic women over 35 with a discrete palpable breast lump were assessed in a dedicated multidisciplinary clinic, Aug 1989Apr 1991. For a lump to be left in situ the following criteria had to be fulfilled: 1. Clinically lump feels entirely benign 2. Mammography and/or ultrasound benign 3. 2 fine needle aspirations (FNA) showing benign cytology 4. If 1-3 fulfilled, but lump >3cm excision advised 146 lumps were simple cysts; these resolved completely on aspiration. 142 were solid 105 women fulfilled the above criteria: 16 chose operation (histology, benign). 37 women failed the criteria and proceeded to excision biopsy.