Larger Primary Tumor Size Research Articles

Low Expression of Bax Predicts Poor Prognosis in Resected Non-small Cell Lung Cancer Patients with Non-squamous Histology

ObjectiveThe present study evaluated the prognostic significance of apoptosis-related proteins p53, Bax and galectin-3 in patients with non-small cell lung cancer (NSCLC) treated with surgical resection.MethodsWe investigated the expression of these proteins and their association with clinicopathologic characteristics including disease-free survival (DFS) and overall survival (OS) in 205 NSCLC patients who underwent surgical resection (Stage I, 97; II, 46; IIIA, 45; IIIB, 17) using immunohistochemistry. Eighty-eight patients (43%) received adjuvant treatment (chemotherapy: 8, radiotherapy: 24, both: 56).ResultsHigh expressions of Bax, p53 and galectin-3 were observed in 48 (23%), 81 (40%) and 105 (51%) patients, respectively. Low expression of Bax was significantly associated with male gender, squamous cell histology and low expression of galectin-3. Five-year DFS and OS of total patients were 37 and 46%, respectively. High expressions of p53 and galectin-3 were not associated with poor DFS or OS, and no significant correlation existed between low expression of Bax and outcome of patients. However, in patients with non-squamous histology (108 patients), low expression of Bax was a significant independent predictor of poor DFS (P = 0.017) and OS (P = 0.037). In addition, in patients with Stage II or III disease, low expression of Bax significantly correlated with poor DFS (P = 0.004). It was also the most significant independent poor prognostic factor second only to a large primary tumor size in Stage II or III patients with non-squamous histology.ConclusionsLow expression of Bax was significantly associated with poor prognosis in resected NSCLC patients with non-squamous histology.

Malignant Phyllodes Tumor of the Breast: Local Control Rates With Surgery Alone

Patients with malignant phyllodes tumors of the breast (MPTB) are routinely treated with surgery alone. We performed a retrospective study to determine local control rates based on tumor size and type of surgery performed. We reviewed records of 478 patients with MPTB treated between March 1964, and August 2005. The data were extracted from the IMPAC National Oncology Database consisting of merged tumor registries from 130 hospitals. Median follow-up was 64 months (range, 0-410 months). Actuarial 5-year local control rates were 79.4% for 169 lumpectomy patients and 91.2% for 207 mastectomy patients treated by surgery alone. Five-year local control rates for lumpectomy based on tumor size were 91% for 0-2 cm tumors, 85% for 2-5 cm tumors, and 59% for 5-10 cm tumors. For mastectomy patients, 5-year local control rates were 100% for 0-2 cm tumors, 95% for 2-5 cm tumors, 88% for 5-10 cm tumors, and 85% for 10-20 cm tumors. Multivariate analysis of overall survival found several factors to be significant including advancing age with each decade after 50 years of age, appearance of distant metastases, larger primary tumor size, and local control vs. local recurrence (Hazard Ratio [HR] 2.5, p < 0.05). Malignant phyllodes tumors of the breast local recurrence rates are 15% or greater for patients with tumors >2 cm treated by lumpectomy alone and tumors >10 cm treated by mastectomy alone. Adjuvant radiation therapy should be evaluated for these patients. This may be especially important because our study showed that local recurrence impacted on survival rates.

The importance of distant metastases in hormone-sensitive breast cancer

Breast cancer is a leading cause of cancer death in women worldwide. Survival from breast cancer is improving, but distant metastases remain the most common type of breast cancer recurrence, resulting in more than 40,000 deaths per year in the USA alone. Distant metastases are associated with the poorest outcomes when compared with loco-regional or contralateral recurrences and are also associated with greater health care costs and diminished quality of life. The risk of distant metastases increases with larger primary tumor size, lymph node positive cancer, higher tumor grade, and prior loco-regional recurrence. Yet, even patients with minimal risk factors may develop distant metastases. Thus, reducing the development of such relapses is an important goal in adjuvant therapy. As the development of distant metastases has been consistently associated with eventual mortality from breast cancer, a reduction in distant metastases may serve as a better surrogate marker for overall survival and provide earlier results from clinical trials testing new types of adjuvant therapy.

Expanding the Indications for Sentinel Lymph Node Surgery in Breast Cancer

Nodal evaluation in breast cancer patients is important for staging and continues to be the strongest indicator of breast cancer outcome. This information is used to make treatment decisions, including chemotherapy and radiation therapy, in individual patients. The removal of lymph nodes that contain metastatic disease also plays a role in local–regional control. Historically, this has been performed with an axillary lymph node dissection (ALND). Over the last 15 years, sentinel lymph node (SLN) surgery has been established as a replacement for ALND in patients with breast cancer and its use and indications are expanding. SLN surgery was described initially in the management of patients with clinically node-negative melanoma and was translated into the breast cancer population in the early 1990s by Krag [1] and Guiliano [2]. The benefits of SLN surgery are that it can avoid the need for ALND in node-negative patients and result in a decreased complication rate compared with ALND, particularly in terms of the development of lymphedema, impaired shoulder mobility and paresthesias [3,4]. Initially, its use was limited to patients with T1 or T2 tumors and a clinically negative axilla. Relative contraindications for the use of this technique have included large primary tumor size, inflammatory breast cancer, multifocal or multicentric disease, use of preoperative chemotherapy, prior breast or axillary surgery of any kind, previous breast augmentation or breast reduction surgery, and pregnancy. As our experience with SLN surgery has evolved, the identification rate of SLNs at surgery has improved and false-negative rates have decreased. A review of the published literature demonstrates that the identification rate of the SLN ranges from 90–95% and the false-negative rate of SLN surgery varies between 5–10%. The procedure is either performed with the use of radioisotope, blue dye or both. The most commonly used blue dye is isosulfan blue dye (LymphazurinTM), although methylene blue is used in some centers. The consensus statement by the American Society of Breast Surgeons advocates that the radioactive tracer and the blue dye are both used to increase the identification rate and decrease the false-negative rate of SLN surgery. A SLN is defined as a node which is radioactive, blue or palpably abnormal. The indications for SLN surgery are expanding as experience with SLN surgery grows and evidence regarding the feasibility and accuracy of SLN surgery in various different patient subgroups becomes available.

Low expression of bax predicts poor prognosis in resected non-small cell lung cancer patients with nonsquamous histology

7215 Background: Both p53 and bax proteins are known to promote apoptosis, and decreased expression of bax and mutation of p53 have been associated with poor progosis in several malignancies. Methods: We investigated the expression of these proteins and their association with clinicopatholgic characteristics including disease-free survival (DFS) and overall survival (OS) in 209 non-small cell lung cancer (NSCLC) patients (pts) who underwent surgical resection (stage I: 97, II: 46, IIIA: 45, IIIB: 17, IV: 4) using immunohistochemistry. Ninety-one pts (44%) received adjuvant treatment (chemotherapy: 9, radiotherapy: 24, both: 58). Results: While 82 pts (39%) had overexpression of p53 (&gt;50% tumor cells positive), low expression of bax (no or weak staining in intensity) was observed in 159 pts (76%), which was significantly associated with male gender (p &lt; 0.0001), squamous cell carcinoma (p &lt; 0.0001), and overexpression of p53 (p = 0.028). With a median follow-up of 65 months (34–133 months) in survivors, 5-year DFS and OS of total pts were 38% and 46%, respectively, excluding 7 deaths from postoperative complications. Neither overexpression of p53 nor low expression of bax was associated with poor DFS (p = 0.728, p = 0.335) and OS (p = 0.927, p = 0.261). However, in pts with nonsquamous histology (111 pts), low expression of bax was significant independent predictor of poor DFS (p = 0.004) in addition to advanced stage (p &lt; 0.0001) and large primary tumor size (&gt;4 cm) (p = 0.005) in multivariate analysis. Furthermore, low expression of bax was associated with poor OS (p = 0.048) along with advanced stage (p = 0.01) and pneumonectomy (p = 0.003). Conclusions: Low expession of bax was significantly associated with poor prognosis in NSCLC pts with nonsquamous histology. No significant financial relationships to disclose.

Loco-regional recurrence after mastectomy in high-risk breast cancer—risk and prognosis. An analysis of patients from the DBCG 82 b&c randomization trials

Background and purpose In the DBCG 82 b&c trials, 3083 patients with stages II and III breast cancer were randomised to receive post-mastectomy radiotherapy (RT) versus no RT in addition to systemic therapy. The study showed a decrease in loco-regional recurrences and an improved survival in patients receiving RT. The aim of the present study was to identify risk factors for loco-regional recurrence (LRR), to evaluate the treatment of LRR and to examine the prognosis after LRR. Patients and methods The 18-year probabilities of LRR were calculated for different prognostic factors using the Kaplan–Meier method. The efficacy of different LRR treatments was compared. The 5-year survival and distant metastases (DM) probability after LRR was calculated with regard to initial randomization group, primary tumor and recurrence related variables. Results Of the 3083 patients, 535 had a LRR alone as first site of failure. In univariate analyses, large primary tumor size, ductal carcinoma, high malignancy grade, fascia invasion, few removed nodes, many positive nodes and extracapsular invasion were all risk factors for developing LRR. Combined treatment with surgery and RT at the time of LRR increased the persistent loco-regional control. The 5-year probability of subsequent DM was 73% irrespective of initial randomization group. In multivariate analysis, large primary tumor size, many positive nodes, extracapsular invasion, supra/infraclaviculary failures, multiple LRR and a short interval less than 2 years to first LRR were poor prognostic factors for survival. Conclusions Twenty-seven percent of LRR patients had no DM 5 years after failure. Initial randomization group did not alter the prognosis after LRR. Combined treatment of the LRR with surgery and RT improved persistent loco-regional control compared with surgery or RT alone.

Clinicopathologic review of malignant polyps in stage 1A carcinoma of the endometrium

Objectives. The aims of this study were to determine the incidence of malignant polyps in stage 1A endometrial cancer, to define the pathological features of such cancers, and to assess whether clinical outcome differs from similar cancers without a malignant polyp. Methods. We performed a retrospective pathological review of 107 cases of stage 1A endometrial cancer treated at two centers in New South Wales between January 1988 and July 2003. The presence of a malignant polyp was determined and a pathological description made of the tumor. Clinical data were collected, including prior tamoxifen usage, tumor recurrence and survival. The outcome of the malignant polyp group was compared to the same histological subtype not involving a malignant polyp. Results. The incidence of malignant polyps in our series was 32%. Malignant polyps occurred in all 8 cases involving a serous subtype. Precursor lesions of endometrial cancer were identified within malignant polyps. Three out of the four recurrences occurred in high-grade tumor subtypes and all four had a large primary tumor (size ≥ 4 cm). When comparing the same subtype of tumor with and without a malignant polyp, there was no significant difference in clinical outcome. Conclusions. Approximately one-third of stage 1A endometrial cancers are associated with a malignant polyp. Serous carcinoma commonly arises within an otherwise benign endometrial polyp. Malignant polyps offer an opportunity to identify precursors of endometrial carcinoma. Clinical outcome of stage 1A endometrial carcinoma was related to the histological subtype and the size of the tumor rather than the presence of a malignant polyp.

Expression of galectin-3 in non-small cell lung cancer (NSCLC): Prognostic significance in adenocarcinoma

9671 Background: Expression of galectin-3, which belongs to a family of galactoside-binding proteins, has been associated with malignant transformation, cancer progression, and protection against apoptosis in several malignancies such as breast cancer. Methods: We investigated the expression of galectin-3 and its association with clinicopatholgic characteristics including disease-free survival (DFS) and overall survival (OS) in 104 patients (pts) with locally advanced NSCLC who underwent surgical resection (stage II: 47, IIIA: 40, IIIB: 10, IV: 7) using immunohistochemistry. Eighty-two pts (79%) received adjuvant treatment (chemotherapy: 9, radiotherapy: 17, both: 56). Results: High expression of galectin-3 was observed in 46 pts (44%), which was significantly associated with adenocarcinoma (p=0.001) and large primary tumor size (>4 cm) (p=0.033). With a median follow-up of 45 months (20–114 months) in survivors, 4-year DFS and OS of total pts were 31% and 43%, respectively, excluding 6 deaths from postoperative complications. High expression of galectin-3 was not associated with poor DFS (p=0.233) or OS (p=0.391). However, in pts with adenocarcinoma (36 pts) or adenosquamous carcinoma (7 pts), high expression of galectin-3 was significant independent predictor of poor DFS (p=0.021) in addition to male gender (p=0.026) and advanced stage (p=0.013). Conclusions: High expression of galectin-3 was significantly associated with poor DFS in locally advanced NSCLC pts with adenocarcioma. No significant financial relationships to disclose.

Stage II testicular seminoma: Patterns of recurrence and outcome of treatment: Chung PW, Gospodarowicz MK, Panzarella T, Jewett, MAS, Sturgeon JFG, Tew-George B, Bayley AJS, Catton CN, Milosevic MF, Moore M, Warde PR, Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.

To review treatment outcome and patterns of failure for patients with stage II testicular seminoma and to identify prognostic factors for relapse. From 1981 to 1999, 126 men with stage II seminoma were treated at Princess Margaret Hospital. Of these, 95 were treated with radiotherapy (RT) and 31 with chemotherapy (ChT). Patient and tumour characteristics were analyzed for prognostic significance for subsequent relapse. At median follow-up of 8.5 years, the 5- and 10-year overall survival were both 93%, the 5- and 10-year cause-specific survival were both 94% and the 5- and 10-year relapse-free rates were both 85%. Patients with stage IIA and IIB disease treated with RT and stage IIB treated with chemotherapy had 5-year relapse-free rates of 91.7%, 89.7% and 83.3%, respectively. Seventeen percent of patients treated with radiotherapy and 6% of those treated with chemotherapy have relapsed. Of the RT patients the commonest sites of relapse were left supraclavicular fossa, lung/mediastinum, bone, para-aortics and liver; nine patients had a solitary site of relapse. Two patients treated with chemotherapy had recurrence in the para-aortic and iliac nodes. For RT patients, larger primary tumour size was associated with a reduction in relapse rate. Age, rete testis invasion and lymphovascular invasion were found not to be of prognostic significance. In stage IIA/B seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Chemotherapy is the treatment of choice for stage IIC seminoma.

Prognostic significance of nm23-H1 expression in oral squamous cell carcinoma.

Recent studies indicated nm23-H1 played a role in cancer progression. Therefore, we investigated clinical significance of nm23-H1 expression in oral squamous cell carcinoma (OSCC). In total, 86 OSCC specimens were immunohistochemically stained with nm23-H1-specific monoclonal antibodies. Immunohistochemical staining of nm23-H1 was confirmed by immunoblotting. The relations between nm23-H1 expression and clinicopathologic variables were evaluated by χ2 analysis. As increased size of primary tumour could escalate metastatic potential and the data of patients at the late T stage might confound statistical analyses, we thus paid special attention to 54 patients at the early T stage of OSCC. Statistical difference of survival was compared by a log-rank test. Immunohistochemically, nm23-H1 expression was detected in 48.8% (42 out of 86) of tumorous specimens. It positively correlated with larger primary tumour size (P=0.03) and inversely with cigarette-smoking habit (P=0.042). In patients at the early T stage, decreased nm23 expression was associated with increased incidence of lymph node metastasis (P=0.004) and indicated poor survival (P=0.014). Tumour nm23-H1 expression is a prognostic factor for predicting better survival in OSCC patients at the early T stage, which may reflect antimetastatic potential of nm23. Therefore, modulation of nm23-H1 expression in cancer cells can provide a novel possibility of improving therapeutic strategy at this stage. In addition, our results further indicated cigarette smoking could aggravate the extent of nm23-H1 expression and possibly disease progression of OSCC patients.

Stage II testicular seminoma: patterns of recurrence and outcome of treatment.

To review treatment outcome and patterns of failure for patients with stage II testicular seminoma and to identify prognostic factors for relapse. From 1981 to 1999, 126 men with stage II seminoma were treated at Princess Margaret Hospital. Of these, 95 were treated with radiotherapy (RT) and 31 with chemotherapy (ChT). Patient and tumour characteristics were analyzed for prognostic significance for subsequent relapse. At median follow-up of 8.5 years, the 5- and 10-year overall survival were both 93%, the 5- and 10-year cause-specific survival were both 94% and the 5- and 10-year relapse-free rates were both 85%. Patients with stage IIA and IIB disease treated with RT and stage IIB treated with chemotherapy had 5-year relapse-free rates of 91.7%, 89.7% and 83.3%, respectively. Seventeen percent of patients treated with radiotherapy and 6% of those treated with chemotherapy have relapsed. Of the RT patients the commonest sites of relapse were left supraclavicular fossa, lung/mediastinum, bone, para-aortics and liver; nine patients had a solitary site of relapse. Two patients treated with chemotherapy had recurrence in the para-aortic and iliac nodes. For RT patients, larger primary tumour size was associated with a reduction in relapse rate. Age, rete testis invasion and lymphovascular invasion were found not to be of prognostic significance. In stage IIA/B seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Chemotherapy is the treatment of choice for stage IIC seminoma.

Prognostic value of p53 expression and histopathological parameters in squamous cell carcinoma of oral tongue.

The TNM staging system is helpful but not enough to determine prognosis of the patients with squamous cell carcinoma of the oral tongue. T-stage alone is not suggestive for prediction of occult nodal metastases. For this reason, histopathological examination of 70 patients with squamous cell carcinoma of the oral tongue was done retrospectively. The histological differentiation, tumour thickness, perineural and lymphovascular space invasions, the amount of lymphocyte infiltration and pattern of tumour invasion were examined. Immunohistochemical examination was used to determine p53 immunoreactivity as well. The effect of these histopathological parameters and p53 immunoreactivity on nodal metastases and locoregional recurrence were analyzed using the chi-squared test. In terms of nodal metastases the only statistically significant difference between the two groups was tumour thickness, either < 9 mm or > 9 mm (p < 0.05, chi 2 = 17.182). Tumour thickness, perineural invasion, lymphovascular space invasion, the amount of lymphocyte infiltration all correlated statistically with locoregional recurrence (p < 0.05, chi 2 = 6.293 for tumour thickness; p < 0.06, p = 0.054 for perineural invasion; p < 0.05, chi 2 = 8.689 for lymphovascular space invasion; p < 0.05, chi 2 = 5.320 for lymphocyte infiltration). The immunoreactivity of p53 correlated significantly with larger primary tumour size (p < 0.05, chi 2 = 5.440, lymph node metastases (p < 0.05, chi 2 = 4.093) and with pathological tumour stage (p < 0.05, chi 2 = 5.713). These results reveal that the above-mentioned histological parameters and p53 determination could be used for handling a specimen from an anterior tongue squamous cell carcinoma.

Detection of occult breast cancer micrometastases in axillary lymph nodes using a multimarker reverse transcriptase-polymerase chain reaction panel

Background: Axillary lymph node status in breast cancer patients remains the single most important predictor of outcomes. Current methods of histopathologic analysis may be inadequate because 30% of node-negative patients recur. The purpose of this study was to test the hypothesis that a multigene reverse transcriptase-polymerase chain reaction (RT-PCR) panel provides a more sensitive method to detect axillary lymph node metastases than routine pathologic examination. Study Design: Sixty-one consecutive breast cancer patients were evaluated, with nine normal control patients. Nodes > 1 cm were bisected for histopathologic and RT-PCR analysis. Nodal tissue was homogenized, and total RNA was converted into cDNA with reverse transcriptase. Reverse transcriptase-polymerase chain reaction analysis was performed with primers specific for keratin-19, c-myc, prolactin inducible protein (PIP), and β-actin using ethidium bromide gel electrophoresis. Reverse transcriptase-polymerase chain reaction positive/pathology negative axillary lymph nodes were reevaluated using step sectioning and immunohistochemical staining. Results: Thirty-seven patients had pathologically negative axillary lymph nodes, of which 15 (40%) were positive by RT-PCR analysis. Two RT-PCR negative results (one probably from tissue processing error and the other secondary to sampling error) among the 24 histologically positive specimens were detected (8%). The number of patients in each pathologic stage was 26 patients in stage I; 18, stage IIA; 7, stage IIB; 7, stage IIIA; 3, stage IIIB; and 0 patients in stage IV. By RT-PCR staging, 8 of 26 patients went from stage I to IIA (30%), and 7 of 18 from stage IIA to IIB (39%). Of the RT-PCR positive individuals who were stage I by pathologic analysis, 100% were found to be c-myc positive, 0% keratin-19 positive, and 0% PIP positive; for stage IIIB patients these markers were 50%, 100%, and 100% respectively. Additionally, an increasing number of positive markers per specimen appeared to correlate with larger primary tumor size (p < 0.01) and decreased predicted 5-year survival (r = 0.950, p < 0.002). Conclusions: Multimarker RT-PCR analysis appears to be a readily available and highly sensitive method for the detection of axillary lymph node micrometastases. Longterm followup of RT-PCR positive patients will be required to determine its clinical relevance. If validated as a predictor of disease recurrence, this method would provide a powerful complement to routine histopathologic analysis of axillary lymph nodes.

Papillary thyroid cancer in Saudi Arabia. Clinical, pathologic, and management characteristics.

During a 3-year period, 233 patients with papillary thyroid cancer were seen at King Faisal Specialist Hospital (KFSH) (79% were female; 94% were national subjects). Pathology revealed 88% pure papillary carcinoma and 12% mixed papillary and follicular carcinoma, 7% microfocus, 18% well encapsulated, 24% capsular invasion, and 51% soft tissue invasion. Thirty percent of patients who had initial surgery not done at KFSH compared with 93% of patients who had initial surgery done at KFSH had an I-123 24-hour uptake < 5%. One hundred seventeen patients required completion thyroidectomy at KFSH for significant residual thyroid tissue, 56% of those had residual papillary carcinoma. The amenability of papillary thyroid cancer for cure necessitates the optimization of management at the national level. In Saudi Arabia, papillary thyroid cancer presented in an advanced stage, especially in males as manifested by the large primary tumor size, advance pathologic staging, and distant metastases at the time of presentation. Findings at second surgery, showed significant residual disease.

Delayed diagnosis and large size of breast cancer after a false negative mammogram

The aim of this prospective, multicentre study was to investigate the effects of a false negative mammogram on treatment delay and tumour size. Among 306 consecutive women with histologically diagnosed, invasive breast cancer, the frequency of a false negative mammogram was small (13%) among women aged over 50 years, but 35% among those aged 50 or younger ( P < 0.0001). Forty-five per cent of the women with a false negative mammogram had a longer than 2-month and 29% a longer than 6-month interval from mammography to surgery as compared with only 2 and 0% of women, respectively, who had a true positive mammogram ( P < 0.0001 for both). Women with a false negative mammogram and a longer than 2-month interval to surgery had larger primary tumour size (60 versus 26% pT2-4, P = 0.005) and more often positive axillary nodes (60% versus 32% pN+, P = 0.03) at the time of surgery than those with a shorter delay. We conclude that a false negative mammogram is common in women younger than 50, and may lead to treatment delay and advanced clinical stage.

Cathepsin D expression detected by immunohistochemistry has independent prognostic value in axillary node-negative breast cancer.

Increased expression of the lysosomal protease cathepsin D (CD) has been implicated in the metastatic progression of breast cancer. This study was designed to determine the prognostic significance of CD expression in axillary node-negative (ANN) breast cancer. The relationship of CD expression and onset of soft tissue recurrences and visceral metastatases was also studied. We analyzed a population-based group of 262 ANN breast cancer patients, none of whom had received any adjuvant chemotherapy or endocrine therapy. An immunohistochemical method based on a new monoclonal antibody (1C11) with a distinct epitope specificity made it possible to study CD expression from archival paraffin-embedded specimens and to distinguish staining in tumor cells from the high-level expression found in tumor-infiltrating macrophages. High-level CD expression, as defined by cytoplasmic immunoreactivity in greater than 10% of the cancer cells, was found in 95 cases (36%). High-level CD expression was associated with large primary tumor size (P = .014), but not with histologic grade, estrogen and progesterone receptors, DNA index, or S-phase fraction, or with c-erbB-2 and p53 overexpression. Patients with CD-positive tumors developed significantly more often both soft tissue recurrences and visceral metastases (P = .0007) and had a significantly shorter disease-free survival (P < .0001). Eight-year overall survival of patients with high-level CD expression was 64% as compared with 90% in those with low-level expression (relative risk, 2.97; 95% confidence interval [Cl], 1.6 to 4.4; P < .0001). According to a Cox multivariate model and a regression-tree analysis, high-level CD expression was an independent predictor of poor overall survival in conjunction with tumor size and S-phase fraction. These results indicate that CD expression determined by immunohistochemistry is a powerful prognostic factor in ANN breast cancer. The most significant prognostic information was obtained when CD expression (predicting metastatic activity) was combined with estimate of cell-proliferation rate (S-phase fraction).

DNA index and S-phase fraction and their combination as prognostic factors in operable ductal breast carcinoma

The prognostic significance of DNA ploidy, DNA index (DI), and S-phase fraction (SPF) and their various combinations were studied together with 16 other clinicopathologic factors in 222 patients with operable invasive ductal breast carcinoma. The patients have been followed for a minimum of 22 years after the diagnosis or until death. Nuclear DNA content was determined by flow cytometry from paraffin-embedded tissue. Patients with DNA diploid cancer (n = 57, 26%) had better survival rate corrected for intercurrent deaths than patients with nondiploid cancer (P = 0.002), and also, a small SPF (less than or equal to 14%, calculated in 134 cases) was associated with a favorable outcome in a univariate analysis (P = 0.01). The prognostic value of the DI and SPF was increased if they were combined. The most effective combination was obtained if diploid cancers were grouped together with DNA aneuploid cancers with a DI less than 2.1 and an SPF less than 14%. This combination had considerable prognostic value in a univariate analysis (P = 0.0002) and had independent prognostic value (P = 0.04) in Cox's multivariate analysis together with the primary tumor size (P less than 0.001) in axillary node negative patients but not in axillary node positive patients. In the whole series the presence of axillary nodal metastases (P less than 0.001), high mitotic count (P less than 0.001), a large primary tumor size (P = 0.001), poorly circumscribed tumor margin (P = 0.005), and slight or absent tubule formation (P = 0.05) were the only independent prognostic factors in a multivariate analysis.